Towards a Functional Neuromarker of Impulsivity: Feedback-Related Brain Potential during Risky Decision-Making Associated with Self-Reported Impulsivity in a Non-Clinical Sample.

Risk-taking is part of the multidimensional nature of impulsivity, consisting of an active engagement in behaviors or choices with potentially undesirable results, with probability as the cost for an expected reward. In order to understand the neurophysiological activity during risky behavior and its relationship with other dimensions of impulsivity, we have acquired event-related-potential (ERP) data and self-reported impulsivity scores from 17 non-clinical volunteers. They underwent high-resolution electroencephalography (HR-EEG) combined with an adapted version of the Balloon Analogue Risk Task (BART), and completed the Barratt Impulsiveness Scale (BIS-10) and the Urgency, Premeditation, Perseverance, Sensation Seeking, Impulsive Behavior Scale (UPPS). The ERP components were sensitive to valence (FRN, P300) and risk/reward magnitude (SPN, RewP). Our main finding evidenced a positive correlation between the amplitude of the P300 component following positive feedback and both the global UPPS score and the (lack of) perseverance UPPS subscale, significant for several adjacent electrodes. This finding might suggest an adaptive form of impulsive behavior, which could be associated to the reduction on the difference of the P300 amplitude following negative and positive feedback. However, further investigation with both larger clinical and non-clinical samples is required.

Repetitive Transcranial Magnetic Stimulation as an Add-On Treatment for Cognitive Impairment in Alzheimer's Disease and Its Impact on Self-Rated Quality of Life and Caregiver's Burden.

Alzheimer's disease (AD) is associated with progressive memory loss and decline in executive functions, as well as neuropsychiatric symptoms. Patients usually consider quality of life (QoL) and mood as more important for their health status than disease-specific physical and mental symptoms. In this open-label uncontrolled trial, 12 subjects diagnosed with AD underwent 10 sessions of repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (10 Hz, 20 min, 2000 pulses/day, 110% MT). Outcomes were measured before and 30 days after treatment. Our primary objective was to test the efficacy of rTMS as an add-on treatment for AD on the global cognitive function, assessed through the Mini-Mental State Examination (MMSE) and the Mattis Dementia Rating Scale (MDRS). As secondary objectives, the detailed effect on cognitive functions, depression and anxiety symptoms, QoL, and functionality in daily life activities were evaluated, as well as correlations between QoL and cognition, depression and anxiety scores. The treatment significantly enhanced semantic memory and reduced anxiety. Improvement of these features in AD could become an important target for treatment strategies. Although limited by its design, this trial may contribute with another perspective on the analysis and the impact of rTMS on AD.

Influence of Transcranial Direct Current Stimulation on Psychomotor Symptoms in Major Depression.

BACKGROUND: Transcranial direct current stimulation (tDCS) applied to the left dorsolateral prefrontal cortex (dlPFC) might be a promising treatment strategy for depression. As disturbances in psychomotor activity are one of the key features of unipolar depression are, we aimed to evaluate the behavioral effects of ten tDCS sessions over a 5-day period on psychomotor retardation in depressed patients. METHODS: Twenty-three treatment-resistant depressed patients received either active or sham anodal tDCS to the left dorsolateral prefrontal cortex (2 mA, 10 sessions over 1 week). Psychomotor functioning was registered by means of observer ratings (Salpêtrière Retardation Rating Scale-SRRS) and objective measures (kinematical analysis of movements, automatic imitation). RESULTS: tDCS sessions resulted in improvements on SRRS scores, although active tDCS was not significantly superior to sham tDCS on the kinematical parameters. Furthermore, no general additional antidepressant effect of tDCS was observed. The relatively small sample size and the short periods of observation should be considered when interpreting these results. CONCLUSION: tDCS did not induce a clinically relevant effect on psychomotor function in active and sham stimulation groups.

Can transcranial direct current stimulation (tDCS) improve impulsivity in healthy and psychiatric adult populations? A systematic review.

Impulsivity is a multidimensional phenomenon that remains hard to define. It compounds the core pathological construct of many neuropsychiatric illnesses, and despite its close relation to suicide risk, it currently has no specific treatment. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique whose application results in cognitive function improvement, both in healthy and psychiatric populations. Following PRISMA recommendations, a systematic review of the literature concerning tDCS's effects on impulsive behaviour was performed using the PubMed database. The research was based on the combination of the keyword 'tDCS' with 'impulsivity', 'response inhibition', 'risk-taking', 'planning', 'delay discounting' or 'craving'. The initial search yielded 309 articles, 92 of which were included. Seventy-four papers demonstrated improvement in task performance related to impulsivity in both healthy and clinical adult populations. However, results were often inconsistent. The conditions associated with improvement, such as tDCS parameters and other aspects that may influence tDCS's outcomes, are discussed. The overall effects of tDCS on impulsivity are promising. Yet further research is required to develop a more comprehensive understanding of impulsivity, allowing for a more accurate assessment of its behavioural outcomes as well as a definition of tDCS therapeutic protocols for impulsive disorders.

Event-Related Potentials (ERP) Indices of Motivation during the Effort Expenditure for Reward Task.

Dynamic and temporal facets of the various constructs that comprise motivation remain to be explored. Here, we adapted the Effort Expenditure for Reward Task, a well-known laboratory task used to evaluate motivation, to study the event-related potentials associated with reward processing. The Stimulus Preceding Negativity (SPN) and the P300 were utilized as motivation indicators with high density electroencephalography. The SPN was found to be more negative for difficult choices compared to easy choices, suggesting a greater level of motivation, at a neurophysiological level. The insula, a structure previously associated with both effort discounting and prediction error, was concomitantly activated during the generation of the SPN. Processing a gain significantly altered the amplitude of the P300 compared to an absence of gain, particularly on centroparietal electrodes. One of the generators of the P300 was located on the vmPFC, a cerebral structure involved in the choice between two positive results and their predictions, during loss processing. Both the SPN and the P300 appear to be reliable neural markers of motivation. We postulate that the SPN represents the strength of the motivational level, while the P300 represents the impact of motivation on updating memories of the feedback.

Behavioral and Neural Arguments of Motivational Influence on Decision Making During Uncertainty.

The scientific world is increasingly interested in motivation, primarily due to the suspected impact on decision-making abilities, particularly in uncertain conditions. To explore this plausible relationship, 28 healthy participants were included in the study and performed decision-making and motivational tasks while their neural activity was recorded. All participants performed the Iowa Gambling Task (IGT) and were split into two groups based on their score, one favorable group with 14 participants who performed advantageously and one undecided group with 14 participants who failed to develop the correct strategy on the IGT. In addition, all participants performed the Effort Expenditure for Reward Task (EEfRT), which defines the motivational level of each participant by the effort that participants agree to do in function of reward magnitudes and probabilities to receive these reward (10, 50, and 90%). The completion of both tasks allowed for the exploration of the relationship between the motivational level and decision-making abilities. The EEfRT was adapted to electroencephalography (EEG) recordings to explore how motivation could influence reward experience. Behavioral results showed no difference in EEfRT performances on the whole task between the two groups' performances on the IGT. However, there was a negative correlation between the difficulty to develop an optimal strategy on the IGT and the percentage of difficult choices at the 90% condition on the EEfRT. Each probability condition has been previously associated to different motivational and emotional states, with the 90% condition associated to the reward sensitivity. This behavioral result leads to the hypothesis that reward sensitivity may induce an inability to develop an optimal strategy on the IGT. Group analysis demonstrated that only the undecided group showed a P300 during the processing of the outcome, whereas the favorable group showed a blunted P300. Similarly, there was a negative correlation between the P300 amplitude and the ability to develop an optimal strategy on the IGT. In conclusion, behavioral and neuronal data provides evidence that the propensity to focus only on the immediate outcomes is related to the development of an inefficient strategy on the IGT, without influence of motivation.

Effects of High Frequency Repetitive Transcranial Magnetic Stimulation (HF-rTMS) on Delay Discounting in Major Depressive Disorder: An Open-Label Uncontrolled Pilot Study.

BACKGROUND: Delay discounting (DD) refers to the decrease of a present subjective value of a future reward as the delay of its delivery increases. Major depressive disorder (MDD), besides core emotional and physical symptoms, involves difficulties in reward processing. Depressed patients often display greater temporal discounting rates than healthy subjects. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique applied in several countries to adult patients with treatment resistant depression. Studies suggest that this technique can be used to modulate DD, but no trial has assessed its effects on depressed patients. METHODS: In this open-label uncontrolled trial, 20 patients diagnosed with MDD and at least stage II treatment resistance criteria underwent 20 HF-rTMS sessions over the dorsolateral prefrontal cortex (dlPFC; 10 Hz, 110% MT, 20 min). Pre-post treatment DD rates were compared. Effects on impulsivity, personality factors, and depressive symptoms were also evaluated. RESULTS: No significant effect of HF-rTMS over the left dlPFC on DD of depressed individuals was observed, although rates seemed to increase after sessions. However, treatment resulted in significant improvement on cognitive impulsivity and depressive symptoms, and was well-tolerated. CONCLUSION: Despite the limitations involved, this pilot study allows preliminary evaluation of HF-rTMS effects on DD in MDD, providing substrate for further research.

Efficacy of transcranial direct current stimulation in reducing impulsivity in borderline personality disorder (TIMBER): study protocol of a randomized controlled clinical trial.

BACKGROUND: Impulsivity is a core feature of borderline personality disorder (BPD) and is closely related to suicide risk and destructive and aggressive behaviors. Although transcranial direct current stimulation (tDCS) has shown its promising effects as an intervention to modulate impulsivity, no study has explored its potential regarding BPD. METHODS/DESIGN: This is a multicenter, crossover, double-blind study comparing active versus sham tDCS (2 mA, 30 min), applied over the dorsolateral prefrontal cortex for five consecutive days in 50 BPD patients. Participants will be assessed for impulsivity, depressive symptoms, and suicide risk. The main efficacy criteria on reduction of impulsivity will be the amplitude variation of one specific evoked potential detected by electroencephalography (EEG) during the balloon analogue risk task. Baseline measures will be compared to scores obtained immediately after sessions, then 12 and 30 days later. DISCUSSION: This study investigates the safety and effects of tDCS, which may have a significant impact on impulsivity in patients with BPD and may be useful to reduce risky behaviors. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03498937 . Registered on 17 April 2018.