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The use of tools to perturb brain activity can generate important insights into brain physiology and offer valuable therapeutic approaches for brain disorders. Furthermore, the potential of such tools to enhance normal behavior has become increasingly recognized, and this has led to the development of various noninvasive technologies that provides a broader access to the human brain. While providing a brief survey of brain manipulation procedures used in the past decades, this review aims at stimulating an informed discussion on the use of these new technologies to investigate the human. It highlights the importance to revisit the past use of this unique armamentarium and proceed to a detailed analysis of its present state, especially in regard to human behavioral regulation. [ABSTRACT FROM AUTHOR]

Stress is an adaptive response with repercussions on the human health. The dorsolateral prefrontal cortex (DLPFC) is thought to be involved in stress regulation by contributing to limit its biological and behavioral pejorative consequences. Here, to investigate the contribution of the DLPFC in stress response, we applied transcranial Direct Current Stimulation (tDCS) over the DLPFC during acute stress exposure in healthy participants. We hypothesized that active tDCS compared to sham would impact top-down control of the DLPFC on goal-directed behavior and hypothalamo–pituitary–adrenal (HPA) axis activity. In a double-blind sham-controlled study, 30 healthy subjects were randomly allocated to receive either active (2 mA, n = 15) or sham tDCS (n = 15) with the anode over the left DLPFC and the cathode over the right DLFPC. During the 30-min stimulation period, participants faced an experimental acute stress paradigm. Changes in goal-directed behavior were measured with a decision-making task. HPA axis reactivity was assessed by repeated measures of salivary cortisol. Acute stress decreased appetite for immediate reward in the sham group (mean - 4.40%; p = 0.017) whereas no significant effect of stress was observed in the active group. During stress exposure, we observed a significant larger elevation of salivary cortisol (p = 0.045; Cohen's d = 0.431) in the sham tDCS group (+179.8%; Standard error of the mean (SEM) = 20.6) than in the active group (+138.5%; SEM = 14.2). Stimulating the DLPFC using bifrontal tDCS may prevent stress-induced acute effects on both biological and behavioral outcomes. [ABSTRACT FROM AUTHOR]

Food has both homeostatic and hedonic components, which makes it a potent natural reward. Food related reward could therefore promote an escalation of intake and trigger symptoms associated to withdrawal, suggesting a behavioral parallel with substance abuse. Animal and human theoretical models of food reward and addiction have emerged, raising further interrogations on the validity of a bond between Substance Use Disorders, as clinically categorized in the DSM 5, and food reward. These models propose that highly palatable food items, rich in sugar and/or fat, are overly stimulating to the brain's reward pathways. Moreover, studies have also investigated the possibility of causal link between food reward and the contemporary obesity epidemic, with obesity being potentiated and maintained due to this overwhelming food reward. Although natural rewards are a hot topic in the definition and categorization of Substance Use Disorders, proofs of concept and definite evidence are still inconclusive. This review focuses on available results from experimental studies in animal and human models exploring the concept of food addiction, in an effort to determine if it depicts a specific phenotype and if there is truly a neurobiological similarity between food addiction and Substance Use Disorders. It describes results from sugar, fat and sweet-fat bingeing in rodent models, and behavioral and neurobiological assessments in different human populations. Although pieces of behavioral and neurobiological evidence supporting a food addiction phenotype in animals and humans are interesting, it seems premature to conclude on its validity. [ABSTRACT FROM AUTHOR]

Abstract: Background: Most tobacco smokers who wish to quit fail to reach their goal. One important, insufficiently emphasized aspect of addiction relates to the decision-making system, often characterized by dysfunctional cognitive control and a powerful drive for reward. Recent proof-of-principle studies indicate that transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) can transiently modulate processes involved in decision-making, and reduce substance intake and craving for various addictions. We previously proposed that this beneficial effect of stimulation for reducing addictive behaviors is in part mediated by more reflective decision-making. The goal of this study was to test whether nicotine intake and decision-making behaviors are modulated by tDCS over the DLPFC in tobacco smokers who wished to quit smoking. Methods: Subjects received two five-day tDCS regimens (active or sham). Stimulation was delivered over the right DLPFC at a 2mA during 30min. Nicotine cravings, cigarette consumption and decision-making were assessed before and after each session. Results: Main findings include a significant decrease in the number of cigarettes smoked when participants received active as compared to sham stimulation. This effect lasted up to four days after the end of the stimulation regimen. In regards to decision-making, smokers rejected more often offers of cigarettes, but not offers of money, after they received active as compared to sham stimulation at the Ultimatum Game. No significant change was observed at the Risk Task with cigarettes or money as rewards. Conclusion: Overall, these findings suggest that tDCS over the DLPFC may be beneficial for smoking reduction and induce reward sensitive effects. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

In the present study we tested the hypothesis that, in subjects with Asperger's syndrome (ASP), the dynamics of language‐related regions might be abnormal, so that repetitive transcranial magnetic stimulation (rTMS) over Broca's area leads to differential behavioral effects as seen in neurotypical controls. We conducted a five‐stimulation‐site, double‐blind, multiple crossover, pseudo‐randomized, sham‐controlled study in 10 individuals with ASP and 10 age‐ and gender‐matched healthy subjects. Object naming was assessed before and after low‐frequency rTMS of the left pars opercularis, left pars triangularis, right pars opercularis and right pars triangularis, and sham stimulation, as guided stereotaxically by each individual's brain magnetic resonance imaging. In ASP participants, naming improved after rTMS of the left pars triangularis as compared with sham stimulation, whereas rTMS of the adjacent left opercularis lengthened naming latency. In healthy subjects, stimulation of parts of Broca's area did not lead to significant changes in naming skills, consistent with published data. Overall, these findings support our hypothesis of abnormal language neural network dynamics in individuals with ASP. From a methodological point of view, this work illustrates the use of rTMS to study the dynamics of brain–behavior relations by revealing the differential behavioral impact of non‐invasive brain stimulation in a neuropsychiatric disorder. [ABSTRACT FROM AUTHOR]

Noninvasive brain stimulation of the dorsolateral prefrontal cortex with repetitive transcranial magnetic stimulation and transcranial direct current stimulation can modify decision-making behaviors in healthy subjects. The same type of noninvasive brain stimulation can suppress drug craving in substance user patients, who often display impaired decision-making behaviors. We discuss the implications of these studies for the cognitive neurosciences and their translational applications to the treatment of addictions. We propose a neurocognitive model that can account for our findings and suggests a promising therapeutic role of brain stimulation in the treatment of substance abuse and addictive behavior disorders. [ABSTRACT FROM AUTHOR]

The observation of an action modulates motor cortical outputs in specific ways, in part through mediation of the mirror neuron system. Sometimes we infer a meaning to an observed action based on integration of the actual percept with memories. Here, we conducted a series of experiments in healthy adults to investigate whether such inferred meanings can also modulate motor cortical outputs in specific ways. We show that brief observation of a neutral stimulus mimicking a hand does not significantly modulate motor cortical excitability (Study 1) although, after prolonged exposure, it can lead to a relatively nonspecific modulation (Study 2). However, when such a neutral stimulus is preceded by exposure to a hand stimulus, the latter appears to serve as a prime, perhaps enabling meaning to the neutral stimulus, which then modulates motor cortical excitability in accordance with mirror neuron-driving properties (Studies 2 and 3). Overall results suggest that a symbolic value ascribed to an otherwise neutral stimulus can modulate motor cortical outputs, revealing the influence of top-down inputs on the mirror neuron system. These findings indicate a novel aspect of the human mirror neuron system: an otherwise neutral stimulus can acquire specific mirror neuron-driving properties in the absence of a direct association between motor practice and perception. This significant malleability in the way that the mirror neuron system can code otherwise meaningless (i.e. arbitrarily associated) stimuli may contribute to coding communicative signals such as language. This may represent a mirror neuron system feature that is unique to humans. [ABSTRACT FROM AUTHOR]

Abstract: Recent advances in social neuroscience suggest a link between empathy and the mirror neuron system (MNS). Impaired empathy is one of the core diagnostic features of psychopathic personality disorder. In the present study, we investigated whether psychopathic personality traits in a non-psychiatric sample were related to MNS function. Healthy participants viewed short videos known to activate the sensorimotor MNS for pain (a needle penetrating a human hand) while transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEP) were recorded as a measure of motor cortex excitability. Individual psychopathic personality traits were assessed using the Psychopathic Personality Inventory (PPI) and correlated with the MEP findings. Consistent with previous data, observation of the painful stimulus was associated with a significant reduction in the amplitude of the TMS-induced MEP. Interestingly, the level of corticospinal excitability modulation was positively correlated with individual scores on the coldheartedness subscale of the PPI, such that individuals with the greatest MEP reduction were the ones scoring highest on the coldheartedness measure. These data suggest the existence of a functional link between ‘motor empathy’ and psychopathy. [Copyright &y& Elsevier]

Studies have shown increased risk taking in healthy individuals after low-frequency repetitive transcranial magnetic stimulation, known to transiently suppress cortical excitability, over the right dorsolateral prefrontal cortex (DLPFC). It appears, therefore, plausible that differential modulation of DLPFC activity, increasing the right while decreasing the left, might lead to decreased risk taking, which could hold clinical relevance as excessively risky decision making is observed in clinical populations leading to deleterious consequences. The goal of the present study was to investigate whether risk-taking behaviors could be decreased using concurrent anodal transcranial direct current stimulation (tDCS) of the right DLPFC, which allows upregulation of brain activity, with cathodal tDCS of the left DLPCF, which downregulates activity. Thirty-six healthy volunteers performed the risk task while they received either anodal over the right with cathodal over the left DLPFC, anodal over the left with cathodal over the right DLPFC, or sham stimulation. We hypothesized that right anodal/left cathodal would decrease risk-taking behavior compared with left anodal/right cathodal or sham stimulation. As predicted, during right anodal/left cathodal stimulation over the DLPFC, participants chose more often the safe prospect compared with the other groups. Moreover, these participants appeared to be insensitive to the reward associated with the prospects. These findings support the notion that the interhemispheric balance of activity across the DLPFCs is critical in decision-making behaviors. Most importantly, the observed suppression of risky behaviors suggests that populations with boundless risk-taking behaviors leading to negative real-life consequences, such as individuals with addiction, might benefit from such neuromodulation-based approaches. [ABSTRACT FROM AUTHOR]

As adult humans, we are continuously faced with decisions in which proper weighing of the risk involved is critical. Excessively risky or overly cautious decision making can both have disastrous real-world consequences. Weighing of risks and benefits toward decision making involves a complex neural network that includes the dorsolateral prefrontal cortex (DLPFC), but its role remains unclear. Repetitive transcranial magnetic stimulation studies have shown that disruption of the DLPFC increases risk-taking behavior. Transcranial direct current stimulation (tDCS) allows upregulation of activity in the DLPFC, and we predicted that it might promote more cautious decision making. Healthy participants received one of the following treatments while they performed the Balloon Analog Risk Task: (1) right anodal/left cathodal DLPFC tDCS, (2) left anodal/ right cathodal DLPFC tDCS, or (3) sham tDCS. This experiment revealed that participants receiving either one of the bilateral DLPFC tDCS strategies adopted a risk-averse response style. In a control experiment, we tested whether unilateral DLPFC stimulation (anodal tDCS over the right or left DLPFC with the cathodal electrode over the contralateral supraorbital area) was sufficient to decrease risk-taking behaviors. This experiment showed no difference in decision-making behaviors between the groups of unilateral DLPFC stimulation and sham stimulation. These findings extend the notion that DLPFC activity is critical for adaptive decision making, possibly by suppressing riskier responses. Anodal tDCS over DLPFC by itself did not significantly change risk-taking behaviors; however, when the contralateral DLPFC was modulated with cathodal tCDS, an important decrease in risk taking was observed. Also, the induced cautious decision-making behavior was observed only when activity of both DLPFCs was modulated. The ability to modify risk-taking behavior may be translated into therapeutic interventions for disorders such as drug abuse, overeating, or pathological gambling. [ABSTRACT FROM AUTHOR]

Abstract: Whereas there is ample evidence for a role of the amygdala in the processing of visual emotional stimuli, particularly those with negative value, discrepant results have been reported regarding amygdala responses to emotional auditory stimuli. The present study used event-related functional magnetic resonance imaging to investigate cerebral activity underlying processing of emotional nonlinguistic vocalizations, with a particular focus on neural changes in the amygdala. Fourteen healthy volunteers were scanned while performing a gender identification task. Stimuli, previously validated on emotional valence, consisted of positive (happiness and sexual pleasure) and negative (sadness and fear) vocalizations, as well as emotionally neutral sounds (e.g., coughs). Results revealed bilateral amygdala activation in response to all emotional vocalizations when compared to neutral stimuli. These findings suggest that the generally accepted involvement of the amygdala in the perception of emotional visual stimuli, such as facial expressions, also applies to stimuli within the auditory modality. Importantly, this amygdala response was observed for both positive and negative emotional vocalizations. [Copyright &y& Elsevier]

Transcranial magnetic stimulation (TMS)-induced virtual lesions in healthy subjects can be used to test neurofunctional models of disease. The interhemispheric rivalry model of heminglect is well suited for such investigations, as simple predictions derived from clinical data can be tested without the caveats normally associated with lesion studies. One of these predictions is that release from contralateral inhibition should lead to increased parietal responsiveness, which, in turn, would enhance spatial attention. Here, we detail studies showing TMS-induced paradoxical functional facilitation of attention in healthy individuals and highlight their contribution to the understanding and treatment of neglect syndromes. [ABSTRACT FROM AUTHOR]

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, pairedpulse 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. [ABSTRACT FROM AUTHOR]

Humans make extensive use of vocal information to attribute emotional states to other individuals. To date, most studies exploring perception of vocal emotions have done so in the context of speech prosody, although nonlinguistic emotional vocalizations represent an important, perhaps more universal, means to express emotions. Here, we explored the perception of emotional nonlinguistic vocalizations in healthy individuals, with an emphasis on potential age- and sex-related differences. Sixty participants rated 563 positive (e.g., laughs, sexual vocalizations), negative (e.g., cries, screams of fear), and neutral vocalizations (e.g., coughs), according to the valence, intensity, and authenticity of the emotion expressed. Ratings were consistent among individuals, suggesting that valence is an adequate measure of emotional categorization. An important effect of age emerged: (a) age by vocalization category interactions were observed for both valence and intensity ratings, and (b) younger participants rated stimuli as more emotional than older individuals (i.e., higher valence for positive, lower for negative, and more intense for both positive and negative). We also found a sex effect in the authenticity ratings: older women rated the vocalizations as less authentic than younger women whereas authenticity judgments did not differ between the two age groups in men. Taken together, these findings suggest that, as previously observed for facial expressions and prosody, the judgments of emotional vocalizations may vary with age. [ABSTRACT FROM AUTHOR]

Recent studies suggested a sensitivity of regions of the human superior temporal sulcus (STS) to the sound of the human voice. However, the question of the species specificity of this response is still open. Healthy adult volunteers were scanned in an event-related fMRI design to compare responses in the STS to human and animal vocalizations, as well as to control nonvocal sounds (e.g., musical instruments). Bilateral activation of anterior STS was observed for human vocalizations, when contrasted with both nonvocal sounds and animal vocalizations. Animal vocalizations, compared to nonvocal sounds, elicited a more restricted left STS activation, although this region responded even more strongly to human vocalizations. This study provides the first evidence suggesting a species specificity in STS responses to vocalizations in humans. [Copyright &y& Elsevier]

The human voice is the carrier of speech, but also an ’auditory face’ that conveys important affective and identity information. Little is known about the neural bases of our abilities to perceive such paralinguistic information in voice. Results from recent neuroimaging studies suggest that the different types of vocal information could be processed in partially dissociated functional pathways, and support a neurocognitive model of voice perception largely similar to that proposed for face perception. [Copyright &y& Elsevier]

The study examined developmental changes in autistic symptoms retrospectively in a sample of 28 verbal children and adolescents with autism. Individuals with Asperger syndrome, PDD-NOS, and related medical conditions were not included in the study. We compared autistic symptoms present at the retrospective assessment and during the 4- to 5-year age period using the ADI-R. Our findings revealed a significant improvement in the three domains relevant for the diagnosis of autism, independent of age or IQ level. Improvement occurred in more symptoms from the social than the communication domain, and for more symptoms from the latter than the restricted interest and repetitive behavior domains. The finding that improvement was not linked to level of functioning and was found in individuals still positive for a diagnosis of autism suggests that improvement belongs to the 'natural history' of the handicap. [ABSTRACT FROM AUTHOR]

Individuals with insomnia present unique patterns of electroencephalographic (EEG) asymmetry between homologous regions of each brain hemisphere, yet few studies have assessed asymmetry within the same hemisphere. Increase in intrahemispheric asymmetry during rapid eye movement (REM) sleep in good sleepers (GS) and disruption of REM sleep in insomnia sufferers (INS) both point out that this activity may be involved in the pathology of insomnia. The objective of the present exploratory study was to evaluate and quantify patterns of fronto-central, fronto-parietal, fronto-occipital, centro-parietal, centro-occipital and parieto-occipital intrahemispheric asymmetry in GS and INS, and to assess their association with sleep-wake misperception, daytime anxiety and depressive symptoms, as well as insomnia severity. This paper provides secondary analysis of standard EEG recorded in 43 INS and 19 GS for three nights in a sleep laboratory. Asymmetry measures were based on EEG power spectral analysis within 0.3–60 Hz computed between pairs of regions at frontal, central, parietal and occipital derivations. Repeated-measures ANOVAs were performed to assess group differences. Exploratory correlations were then performed on asymmetry and sleep-wake misperception, as well as self-reported daytime anxiety and depressive symptoms, and insomnia severity. INS presented increased delta and theta F3/P3 asymmetry during REM sleep compared with GS, positively associated with depressive and insomnia complaints. INS also exhibited decreased centro-occipital (C3/O1, C4/O2) and parieto-occipital (P3–O1, P4/O2) theta asymmetry during REM. These findings suggest that INS present specific patterns of intrahemispheric asymmetry, partially related to their clinical symptoms. Future studies may investigate the extent to which asymmetry is related to sleep-wake misperception or memory impairments. [ABSTRACT FROM AUTHOR]

Previous research reported a priming effect for voices. However, the type of information primed is still largely unknown. In this study, we examined the influence of speaker''s gender and emotional category of the stimulus on priming of non-speech vocalizations in 10 male participants, who performed a gender identification task. We found a significant priming effect, which was greater for female than male vocalizations. In contrast, the emotional category of the stimuli did not appear to modulate the magnitude of priming. These data suggest that different aspects of the information conveyed in non-speech vocalizations may contribute differently to behavioral priming, possibly influenced by task relevance. [Copyright &y& Elsevier]

The notion that manual gestures played an important role in the evolution of human language was strengthened by the discovery of mirror neurons in monkey area F5, the proposed homologue of human Broca's area. This idea is central to the thesis developed by Arbib, and lending further support to a link between motor resonance mechanisms and language/communication development is the case of autism and congenital blindness. We provide an account of how these conditions may relate to the aforementioned theory. [ABSTRACT FROM AUTHOR]

Impairments in social and emotional skills are a defining feature of autism spectrum disorder. Recent research shows that structural and functional abnormalities within the neural system that matches observation and execution of actions — the mirror neuron system — may explain the social aspects of the pathophysiology of autism spectrum disorder. [Copyright &y& Elsevier]

Background Studies have reported that transcranial direct current stimulation (tDCS) can modulate human behaviors, symptoms, and neural activity; however, the neural effects during stimulation are unknown. Most studies compared the effects of tDCS before and after stimulation. The objective of our study was to measure the neurobiological effect of a single tDCS dose during stimulation. Methods We conducted an online and offline protocol combining tDCS and magnetic resonance spectroscopy (MRS) in 17 healthy participants. We applied anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC) and cathodal tDCS over the right DLPFC for 30 minutes, one of the most common montages used with tDCS. We collected MRS measurements in the left DLPFC and left striatum during tDCS and an additional MRS measurement in the left DLPFC immediately after the end of stimulation. Results During stimulation, active tDCS, as compared with sham tDCS, elevated prefrontal N -acetylaspartate and striatal glutamate + glutamine but did not induce significant differences in prefrontal or striatal gamma-aminobutyric acid level. Immediately after stimulation, active tDCS, as compared with sham tDCS, did not significantly induce differences in glutamate + glutamine, N -acetylaspartate, or gamma-aminobutyric acid levels in the left DLPFC. Conclusions These observations indicate that tDCS over the DLPFC has fast excitatory effects, acting on prefrontal and striatal transmissions, and these effects are short lived. One may postulate that repeated sessions of tDCS might induce similar longer lasting effects of elevated prefrontal N -acetylaspartate and striatal glutamate + glutamine levels, which may contribute to its behavioral and clinical effects. [ABSTRACT FROM AUTHOR]

Individuals with schizophrenia display speech and language impairments that greatly impact their integration to the society. The aim of this systematic review was to identify the importance of speech and language therapy (SLT) as part of rehabilitation curriculums for patients with schizophrenia emphasizing on the speech and language abilities assessed, the therapy setting and the therapeutic approach. This article reviewed 18 studies testing the effects of language therapy or training in 433 adults diagnosed with schizophrenia. Results showed that 14 studies out of 18 lead to improvements in language and/or speech abilities. Most of these studies comprised pragmatic or expressive discursive skills being the only aim of the therapy or part of it. The therapy settings vary widely ranging from twice daily individual therapy to once weekly group therapy. The therapeutic approach was mainly operant conditioning. Although the evidence tends to show that certain areas of language are treatable through therapy, it remains difficult to state the type of approach that should be favoured and implemented to treat language impairments in schizophrenia. [ABSTRACT FROM AUTHOR]

Patients with posttraumatic stress disorder (PTSD) display several structural brain differences when compared with healthy individuals. However, findings are particularly inconsistent for soldiers with PTSD. Here, we characterized the brain morphometry of 37 soldiers from the Canadian Armed Forces with adulthood war‐related PTSD using structural magnetic resonance imaging. We assessed time since trauma, as well as PTSD, depressive, and anxiety symptoms with the Modified PTSD Symptoms Scale, Beck Depression Inventory, and Beck Anxiety Inventory, respectively. Whole‐brain morphometry was extracted with FreeSurfer and compared with a validated normative database of more than 2700 healthy individuals. Volume and thickness from several regions differed from the norms. Frontal regions were smaller and thinner, particularly the superior and rostral middle frontal gyri. Furthermore, smaller left rostral middle frontal gyrus, left pericalcarine cortex, and right fusiform gyrus were associated with more recent trauma. All subcortical structures were bigger, except the hippocampus. These findings suggest a particular brain morphometric signature of PTSD in soldiers. Smaller and thinner frontal and larger subcortical regions support impaired top‐down and/or downregulation of emotional response in PTSD. Finally, the correlation of smaller frontal, temporal, and occipital regions with more recent trauma might inform future therapeutic approaches. [ABSTRACT FROM AUTHOR]

Most candidate genes and genetic abnormalities linked to autism spectrum disorders (ASD) are thought to play a role in developmental and experience-dependent plasticity. As a possible index of plasticity, we assessed the modulation of motor corticospinal excitability in individuals with Asperger's syndrome (AS) using transcranial magnetic stimulation (TMS). We measured the modulatory effects of theta-burst stimulation (TBS) on motor evoked potentials (MEPs) induced by single-pulse TMS in individuals with AS as compared with age-, gender- and IQ-matched neurotypical controls. The effect of TBS lasted significantly longer in the AS group. The duration of the TBS-induced modulation alone enabled the reliable classification of a second study cohort of subjects as AS or neurotypical. The alteration in the modulation of corticospinal excitability in AS is thought to reflect aberrant mechanisms of plasticity, and might provide a valuable future diagnostic biomarker for the disease and ultimately offer a target for novel therapeutic interventions. [ABSTRACT FROM AUTHOR]

Abstract: Background: Functional neuroimaging studies have shown that specific brain areas are associated with alcohol craving including the dorsolateral prefrontal cortex (DLPFC). We tested whether modulation of DLPFC using transcranial direct current stimulation (tDCS) could alter alcohol craving in patients with alcohol dependence while being exposed to alcohol cues. Methods: We performed a randomized sham-controlled study in which 13 subjects received sham and active bilateral tDCS delivered to DLPFC (anodal left/cathodal right and anodal right/cathodal left). For sham stimulation, the electrodes were placed at the same positions as in active stimulation; however, the stimulator was turned off after 30s of stimulation. Subjects were presented videos depicting alcohol consumption to increase alcohol craving. Results: Our results showed that both anodal left/cathodal right and anodal right/cathodal left significantly decreased alcohol craving compared to sham stimulation (p <0.0001). In addition, we found that following treatment, craving could not be further increased by alcohol cues. Conclusions: Our findings showed that tDCS treatment to DLPFC can reduce alcohol craving. These findings extend the results of previous studies using noninvasive brain stimulation to reduce craving in humans. Given the relatively rapid suppressive effect of tDCS and the highly fluctuating nature of alcohol craving, this technique may prove to be a valuable treatment strategy within the clinical setting. [Copyright &y& Elsevier]

Abstract: Objectives: Interest in transcranial direct current stimulation (tDCS) in clinical practice has been growing, however, the knowledge about its efficacy and mechanisms of action remains limited. This paper presents a realistic magnetic resonance imaging (MRI)-derived finite element model of currents applied to the human brain during tDCS. Experimental design: Current density distributions were analyzed in a healthy human head model with varied electrode montages. For each configuration, we calculated the cortical current density distributions. Analogous studies were completed for three pathological models of cortical infarcts. Principal observations: The current density magnitude maxima injected in the cortex by 1 mA tDCS ranged from 0.77 to 2.00 mA/cm2. The pathological models revealed that cortical strokes, relative to the non-pathological solutions, can elevate current density maxima and alter their location. Conclusions: These results may guide optimized tDCS for application in normal subjects and patients with focal brain lesions. [Copyright &y& Elsevier]

Little is known regarding the brain substrates of Gambling Disorder, including surface brain morphometry, and whether these are linked to the clinical profile. A better understanding of the brain substrates will likely help determine targets to treat patients. Hence, the aim of this study was two-fold, that is to examine surface-based morphometry in 17 patients with gambling disorder as compared to norms of healthy individuals (2713 and 2790 subjects for cortical and subcortical anatomical scans, respectively) and to assess the clinical relevance of morphometry in patients with Gambling Disorder. This study measured brain volume, surface and thickness in Gambling Disorder. We compared these measures to those of a normative database that controlled for factors such as age and sex. We also tested for correlations with gambling-related behaviors, such as gambling severity and duration, impulsivity, and depressive symptoms (assessed using the South Oaks Gambling Screen, years of gambling, Barratt Impulsiveness Scale, and Beck Depression Inventory, respectively). Patients displayed thinner prefrontal and parietal cortices, greater volume and thickness of the occipital and the entorhinal cortices, and greater volume of subcortical regions as compared to the norms of healthy individuals. There were positive correlations between surface area of occipital regions and depressive symptoms. This work contributes to better characterize the brain substrates of Gambling Disorder, which appear to resemble those of substance use disorders and Internet Gaming Disorder. [Display omitted] • Patients with Gambling Disorder had thinner prefrontal and parietal cortex. • Patients had greater volume and thickness of the occipital and entorhinal cortex. • They also had greater volume of subcortical regions. • This study complements previous literature by using a whole-brain approach. [ABSTRACT FROM AUTHOR]

• The field of NIBS is expanding and adequate training for all NIBS practitioners is needed. • Training should be matched to the responsibilities of Technicians, Clinicians, and Scientists. • We define competencies and propose curricula for TMS and tES organized in Core knowledge, Safety/ethics, Basic Skills, and Advanced Skills. As the field of noninvasive brain stimulation (NIBS) expands, there is a growing need for comprehensive guidelines on training practitioners in the safe and effective administration of NIBS techniques in their various research and clinical applications. This article provides recommendations on the structure and content of this training. Three different types of practitioners are considered (Technicians, Clinicians, and Scientists), to attempt to cover the range of education and responsibilities of practitioners in NIBS from the laboratory to the clinic. Basic or core competencies and more advanced knowledge and skills are discussed, and recommendations offered regarding didactic and practical curricular components. We encourage individual licensing and governing bodies to implement these guidelines. [ABSTRACT FROM AUTHOR]

The article presents a study which investigates the influence of emotion on memory for nonlinguistic vocalizations. In this study, 40 healthy volunteers participated. All participants had normal audition and no history of hearing impairments. Moreover, 72 nonlinguistic vocalizations, each produced by a different speaker, were chosen from a previously validated database. Results show a memory advantage for emotional nonlinguistic vocalizations, compared with neutral ones. The effect was due to the emotionality of the stimuli.

Background: Posttraumatic stress disorder is a debilitating psychiatric disorder characterized by symptoms of intrusive re-experiencing of trauma, avoidance and hyper-arousal. Diagnosis and treatment of PTSD is further complicated by concurrently occurring disorders, the most frequent being major depressive disorder and anxiety disorders. Previous research highlights that attentional processing in posttraumatic stress disorder is associated with substantial interference by emotional stimuli, a phenomenon also observed in these concurrently occurring psychiatric disorders. However, the diagnosis-relevance of this interference remains elusive. Here, we investigated the emotional Stroop interference for diagnosis-related stimuli, generally negative stimuli, and generally positive stimuli in posttraumatic stress disorder, major depressive disorder and anxiety disorders. Methods: We performed a systematic database search in PubMed (Medline), Cochrane Library and PsycINFO on emotional Stroop performance in individuals with a diagnosis of posttraumatic stress disorder, major depressive disorder or anxiety disorders separately. Mean effect sizes, standard errors and confidence intervals were estimated for each clinical group and healthy control group comparison using random effect models. Results: As compared to healthy control group, the posttraumatic stress disorder group displayed greater interference by diagnosis-related stimuli and positive stimuli but not for generally negative stimuli. The major depressive disorder and anxiety disorders groups showed greater interference by diagnosis-related and negative stimuli, but not by positive stimuli. The age and sex had no significant impact on interference. Conclusions: These findings highlight the importance of diagnosis-relevant information on attentional processing in all three clinical populations, posttraumatic stress disorder, major depressive disorder and anxiety disorders. Further, the impact of generally negative stimuli but not generally positive stimuli in major depressive disorder and anxiety disorders indicate impaired attentional bias for mood-congruent stimuli but not for general stimuli. Finally, it remains to be studied whether the influence of generally positive stimuli in posttraumatic stress disorder indicate that positive stimuli are perceived as PTSD related. [ABSTRACT FROM AUTHOR]

Background: Recent studies reported that transcranial direct current stimulation (tDCS) applied over the dorsolateral prefrontal cortex (DLPFC) reduced craving and cigarette smoking. We aimed to evaluate whether 3 sessions of tDCS over the DLPFC modulate cigarette smoking which is a critical factor in tobacco smokers. Methods: In a double-blinded, sham-controlled, parallel experimental study, 22 participants who wished to quit smoking received tDCS with the cathodal over the right DLPFC and anodal over the left DLPFC based on the 10–20 EEG international system (F4, F3) at an intensity of 1.5 mA for 20 minutes during three consecutive days. For sham stimulation, the electrodes placement was the same as for the active stimulation. Results: For the short time interval (8 days after the end of the tDCS regimen), the number of smoked cigarettes was reduced similarly in the active and sham groups (p < 0.001). Also, at the long time-interval (4 months after the end of the tDCS regimen) as compared to pre-tDCS, there was no significant difference in the number of smoked cigarettes in the active (p = 0.806) or the sham (p = 0.573) groups. Overall, there were no statistically significant differences between the active and sham tDCS groups on cigarette smoking. Conclusion: These findings suggested that 3 sessions of tDCS over the right and left DLPFC may reduce number of smoked cigarettes for short-time period but might not be significantly more effective than sham to decrease cigarette smoking. [ABSTRACT FROM AUTHOR]

Gambling disorder is characterized by persistent maladaptive gambling behaviors and is now considered among substance-related and addictive disorders. There is still unmet therapeutic need for these clinical populations, however recent advances indicate that interventions targeting the Glutamatergic/GABAergic system hold promise in reducing symptoms in substance-related and addictive disorders, including gambling disorder. There is some data indicating that transcranial direct current stimulation may hold clinical benefits in substance use disorders and modulate levels of brain metabolites including glutamate and GABA. The goal of the present work was to test whether this non-invasive neurostimulation method modulates key metabolites in gambling disorder. We conducted a sham-controlled, crossover, randomized study, blinded at two levels in order to characterize the effects of transcranial direct current stimulation over the dorsolateral prefrontal cortex on neural metabolites levels in sixteen patients with gambling disorder. Metabolite levels were measured with magnetic resonance spectroscopy from the right dorsolateral prefrontal cortex and the right striatum during active and sham stimulation. Active as compared to sham stimulation elevated prefrontal GABA levels. There were no significant changes between stimulation conditions in prefrontal glutamate + glutamine and N-acetyl Aspartate, or in striatal metabolite levels. Results also indicated positive correlations between metabolite levels during active, but not sham, stimulation and levels of risk taking, impulsivity and craving. Our findings suggest that transcranial direct current stimulation can modulate GABA levels in patients with gambling disorder which may represent an interesting future therapeutic avenue. [ABSTRACT FROM AUTHOR]

Purpose:This proof of concept study tested the ability of a dual task walking protocol using a recently developed avatar-based virtual reality (VR) platform to detect differences between military personnel post mild traumatic brain injury (mTBI) and healthy controls. Methods:The VR platform coordinated motion capture, an interaction and rendering system, and a projection system to present first (participant-controlled) and third person avatars within the context of a specific military patrol scene. A divided attention task was also added. A healthy control group was compared to a group with previous mTBI (both groups comprised of six military personnel) and a repeated measures ANOVA tested for differences between conditions and groups based on recognition errors, walking speed and fluidity and obstacle clearance. Results:The VR platform was well tolerated by both groups. Walking fluidity was degraded for the control group within the more complex navigational dual tasking involving avatars, and appeared greatest in the dual tasking with the interacting avatar. This navigational behaviour was not seen in the mTBI group. Conclusions:The present findings show proof of concept for using avatars, particularly more interactive avatars, to expose differences in executive functioning when applying context-specific protocols (here for the military).Implications for rehabilitationVirtual reality provides a means to control context-specific factors for assessment and intervention.Adding human interaction and agency through avatars increases the ecologic nature of the virtual environment.Avatars in the present application of the Virtual Reality avatar interaction platform appear to provide a better ability to reveal differences between trained, military personal with and without mTBI. [ABSTRACT FROM PUBLISHER]

Substance use disorders (SUDs) can be viewed as a pathology of neuroadaptation. The pharmacological overstimulation of neural mechanisms of reward, motivated learning and memory leads to drug-seeking behavior. A critical characteristic of SUDs is the appearance of craving, the motivated desire and urge to use, which is a main focus of current pharmacological and behavioral therapies. Recent proof-of-concept studies have tested the effects of noninvasive brain stimulation on craving. Although its mechanisms of action are not fully understood, this approach shows interesting potential in tuning down craving and possibly consumption of diverse substances. This article reviews available results on the use of repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (tES) in SUDs, specifically tobacco, alcohol and psychostimulant use disorders. We discuss several important factors that need to be addressed in future works to improve clinical assessment and effects of noninvasive brain stimulation in SUDs. Factors discussed include brain stimulation devices and parameters, study designs, brain states and subjects’ characteristics. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) is a widely used tool for noninvasive modulation of brain activity, that is thought to interact primarily with excitatory and inhibitory neurotransmitter systems. Neurotransmitters such as glutamate and GABA can be measured by magnetic resonance spectroscopy (MRS). An important prerequisite for studying the relationship between MRS neurotransmitter levels and responses to TMS is that both modalities should examine the same regions of brain tissue. However, co-registration of TMS and MRS has been little studied to date. This study reports on a procedure for the co-registration and co-visualization of MRS and TMS, successfully localizing the hand motor cortex, as subsequently determined by its functional identification using TMS. Sixteen healthy subjects took part in the study; in 14 of 16 subjects, the TMS determined location of motor activity intersected the (2.5 cm) 3 voxel selected for MRS, centered on the so called ‘hand knob’ of the precentral gyrus. It is concluded that MRS voxels placed according to established anatomical landmarks in most cases agree well with functional determination of the motor cortex by TMS. Reasons for discrepancies are discussed. [ABSTRACT FROM AUTHOR]

Abstract: Cognitive deficits that are reported in heavy marijuana users (attention, memory, affect perception, decision-making) appear to be completely reversible after a prolonged abstinence period of about 28 days. However, it remains unclear whether the reversibility of these cognitive deficits indicates that (1) chronic marijuana use is not associated with long-lasting changes in cortical networks or (2) that such changes occur but the brain adapts to and compensates for the drug-induced changes. Therefore, we examined whether chronic marijuana smokers would demonstrate a differential pattern of response in comparison to healthy volunteers on a decision-making paradigm (Risk Task) while undergoing sham or active transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC). Twenty-five chronic marijuana users who were abstinent for at least 24h were randomly assigned to receive left anodal/right cathodal tDCS of DLPFC (n =8), right anodal/left cathodal tDCS of DLPFC (n =9), or sham stimulation (n =8); results on Risk Task during sham/active tDCS were compared to healthy volunteers from a previously published dataset. Chronic marijuana users demonstrated more conservative (i.e. less risky) decision-making during sham stimulation. While right anodal stimulation of the DLPFC enhanced conservative decision-making in healthy volunteers, both right anodal and left anodal DLPFC stimulation increased the propensity for risk-taking in marijuana users. These findings reveal alterations in the decision-making neural networks among chronic marijuana users. Finally, we also assessed the effects of tDCS on marijuana craving and observed that right anodal/left cathodal tDCS of DLPFC is significantly associated with a diminished craving for marijuana. [ABSTRACT FROM AUTHOR]

Cognitive performance usually declines in older adults as a result of neurodegenerative processes. One of the cognitive domains usually affected is decision-making. Based on our recent findings suggesting that non-invasive brain stimulation can improve decision-making in young participants, we studied whether bifrontal transcranial direct current stimulation (tDCS) applied over the right and left prefrontal cortex of older adult subjects can change balance of risky and safe responses as it can in younger individuals. Twenty-eight subjects (age range from 50 to 85 years) performed a gambling risk task while receiving either anodal tDCS over the right and cathodal tDCS over the left dorsolateral prefrontal cortex (DLPFC), anodal tDCS over the left with cathodal tDCS over the right DLPFC, or sham stimulation. Our main finding was a significant group effect showing that participants receiving left anodal/right cathodal stimulation chose more often high-risk prospects as compared with participants receiving sham or those receiving right anodal/left cathodal stimulation. This result is contrary to previous findings in young subjects, suggesting that modulation of cortical activity in young and elderly results in opposite behavioral effects; thus supporting fundamental changes in cognitive processing in the elderly. [ABSTRACT FROM AUTHOR]

Abstract: Smoking cue-provoked craving is an intricate behavior associated with strong changes in neural networks. Craving is one of the main reasons subjects continue to smoke; therefore interventions that can modify activity in neural networks associated with craving can be useful tools in future research investigating novel treatments for smoking cessation. The goal of this study was to use a neuromodulatory technique associated with a powerful effect on spontaneous neuronal firing – transcranial direct current stimulation (tDCS) – to modify cue-provoked smoking craving. Based on preliminary data showing that craving can be modified after a single tDCS session, here we investigated the effects of repeated tDCS sessions on craving behavior. Twenty-seven subjects were randomized to receive sham or active tDCS (anodal tDCS of the left DLPFC). Our results show a significant cumulative effect of tDCS on modifying smoking cue-provoked craving. In fact, in the group of active stimulation, smoking cues had an opposite effect on craving after stimulation – it decreased craving – as compared to sham stimulation in which there was a small decrease or increase on craving. In addition, during these 5 days of stimulation there was a small but significant decrease in the number of cigarettes smoked in the active as compared to sham tDCS group. Our findings extend the results of our previous study as they confirm the notion that tDCS has a specific effect on craving behavior and that the effects of several sessions can increase the magnitude of its effect. These results open avenues for the exploration of this method as a therapeutic alternative for smoking cessation and also as a mean to change stimulus-induced behavior. [Copyright &y& Elsevier]

Abstract: We aimed to assess whether modulation of the dorsolateral prefrontal cortex (DLFPC) with noninvasive brain stimulation, namely transcranial direct current stimulation (tDCS), modifies food craving in healthy subjects. We performed a randomized sham-controlled cross-over study in which 23 subjects received sham and active tDCS (anode left/cathode right and anode right/cathode left) of the DLPFC. Subjects were exposed to food and also watched a movie of food associated with strong craving. Desire for food consumption was evaluated by visual analogue scales (VAS) and food consumption before and after treatment. In addition we measured visual attention to food using an eye tracking system. Craving for viewed foods as indexed by VAS was reduced by anode right/cathode left tDCS. After sham stimulation, exposure to real food or food-related movie increased craving; whereas after anode left/cathode right tDCS, the food-related stimuli did not increase craving levels, as revealed by the VAS scale. Moreover, compared with sham stimulation, subjects fixated food-related pictures less frequently after anode right/cathode left tDCS and consumed less food after both active stimulation conditions. These changes were not related to mood changes after any type of tDCS treatment. The effects of tDCS on food craving might be related to a modulation of neural circuits associated with reward and decision-making. [Copyright &y& Elsevier]

Abstract: Objective: The preliminary results of noninvasive brain stimulation for epilepsy treatment have been encouraging, but mixed. Two important factors may contribute to this heterogeneity: the altered brain physiology of patients with epilepsy and the variable presence of antiepileptic drugs. Therefore, we aimed to study the effects of 1Hz rTMS on corticospinal excitability in patients with juvenile myoclonic epilepsy (JME) in two different conditions: low- or high-plasma valproate levels. Methods: Fifteen patients with JME and 12 age-matched healthy subjects participated in this study. Corticospinal excitability before and after 1Hz rTMS was assessed in JME patients with low- and high-plasma valproate levels; and these results were compared with those in healthy subjects. Results: In patients with chronic use of valproate and low-plasma concentrations, 1Hz rTMS had a similar significant inhibitory effect on corticospinal excitability as in healthy subjects. However, in the same patients when the serum valproate concentration was high, 1Hz rTMS increased the corticospinal excitability significantly. In addition, there was a significant positive correlation between plasma valproate levels and the motor threshold changes after 1Hz rTMS. Conclusions: Our findings can be accounted for by mechanisms of homeostatic plasticity and illustrate the dependency of the modulatory effects of rTMS on the physiologic state of the targeted brain cortex. Significance: The therapeutic use of rTMS in epilepsy should take into consideration the interaction between rTMS and drugs that change cortical excitability. [Copyright &y& Elsevier]

Semantic deficits are common in individuals with Alzheimer's disease (AD). These deficits notably impact the ability to understand words. In healthy aging, semantic knowledge increases but semantic processing (i.e., the ability to use this knowledge) may be impaired. This systematic review aimed to investigate semantic processing in healthy aging and AD through behavioral responses and the N400 brain event-related potential. The results of the quantitative and qualitative analyses suggested an overall decrease in accuracy and increase in response times in healthy elderly as compared to young adults, as well as in individuals with AD as compared to age-matched controls. The influence of semantic association, as measured by N400 effect amplitudes, appears smaller in healthy aging and even more so in AD patients. Thus, semantic processing differences may occur in both healthy and pathological aging. The establishment of norms of healthy aging for these outcomes that vary between normal and pathological aging could eventually help early detection of AD. [ABSTRACT FROM AUTHOR]

Background: Tobacco use disorder (TUD) is characterized by the presence of an attentional bias (AB) towards smoking-related stimuli. We investigated whether combining an AB modification paradigm (ABM) with transcranial alternating current stimulation (tACS) applied over the dorsolateral prefrontal cortex (DLPFC) reduces the AB towards smoking-related stimuli, as well as craving level and impulsive choices.Methods: In a sham-controlled, crossover preliminary study, 19 subjects with TUD received two stimulation arms: 1) active tACS (10 Hz, 2 mA, 30 min) combined with ABM and 2) sham tACS combined with ABM, in a randomized order, separated by one week. AB towards smoking cues during passive observation of smoking and neutral cues was assessed with an eye-tracking device and reactions times at a visual-probe task. Craving level was measured with the Questionnaire of Smoking Urges. Impulsive choices were assessed with the delay discounting task.Results: Active tACS combined with ABM reduced the amount of time spent looking at smoking-related pictures (p = 0.03), prevented the increase of self-reported desire to smoke (p = 0.026), and reduced the proportion of impulsive choices (p = 0.049), compared to sham tACS combined with ABM. No significant effects were reported on other craving dimensions and on AB based on reaction times.Conclusions: These preliminary findings suggest that combining tACS with ABM may help smokers who wish to quit by reducing the desire to smoke, attention to smoking-cues, and impulsive decision-making. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]