July Silveira Gomes

Left Dorsolateral Prefrontal Cortex Anodal tDCS Effects on Negative Symptoms in Schizophrenia

Cognitive functions maintained stable (20 at baseline and 24 at the final outcome) as assessed by MOCA, with improvement on memory tasks. MDD symptoms substantially improved during the 10day treatment course and remained stable after three months follow-up, and the patient reported significant global clinical gains (see the Fig. 1). The patient was followed on a monthly basis and no risk issues were observed, such as gestational diabetes or hypertension. Caesarean section was performed opted by the gynecology and obstetrics team due to be considered high-risk pregnancy because of the MDD treatment. No complications during child-birth occurred. The neonate was a healthy full-term, 8 pounds newborn, with APGAR 10/10 and no malformations. The TNS protocol is based on a “bottom up” mechanism [7]. The electric stimuli follows the peripheral nerves pathway through central structures [7] such as the amygdala and the hippocampus, toward higher cortical area such as the dorsolateral prefrontal cortex, previously demonstrated to be involved in MDDwith symptoms amelioration when stimulated with other neuromodulation techniques [8]. Data on the use of cranial nerve stimulation for MDD during pregnancy is scant. In fact, TNS was not evaluated before. Only one case of vagus nerve stimulation (VNS) for the treatment of MDD in pregnancy was performedwith no safety issues [9]. Safety evaluation on the use of VNS in an animal model (pilot study of the teratogenicity) was performed with 10 rabbits with no safety issues reported [10]. We present the first report using TNS in a pregnant patient with successful amelioration of MDD symptoms and no considerable side effects to the newborn. TNS is a focused electrical stimulation technique without likely electric stimulation propagation to the fetus. Our findings are based on a case study, thus having limited generalizability. Nonetheless, these encouraging results should be seen as hypothesis-driven for further controlled, randomized trials exploring the safety and impact of TNS in the treatment of MDD in pregnancy.

Transcranial Direct Current Stimulation Effects on Athletes’ Cognitive Performance: An Exploratory Proof of Concept Trial

Among the 2016 Olympic and Paralympic Games’ unforgettable moments, one could not overlook performances by Phelps and Bolt, which challenge old premises about the maximum extension of individual supremacism in ultracompetitive modalities and the doping scandals. Different media channels resonated these two trends, with an unseen rise on discussions about traits and practices that may set ultrahigh performance athletes apart from the more ordinary ones. Yet, some key issues remain undebated. This paper aims to add to this debate, with a proof of concept trial, which investigates whether transcranial direct current stimulation (tDCS) may serve as an aid for professional athletes. Ten professional athletes of three different modalities (judo, N = 4 athletes, swimming, N = 3 athletes, and rhythmic gymnastics, N = 3 athletes) received anodal stimulation (2 mA) for 20 min on the left dorsolateral prefrontal cortex for ten consecutive weekdays. We observed a positive effect of tDCS in their cognitive performance, including a significant improvement in alternated, sustained, and divided attention and in memory scores. We also observed a decrease in Beck Depression Inventory scores (4.50 points) in this non-clinical population. These preliminary results suggest that tDCS sessions may translate into competitive advantages for professional athletes and recommend the deepening of the discussion on its ethical use in sports, which is ultimately tied to the wider debate around the risks and opportunities that neuromodulation brings to the table.

Transcutaneous Vagus Nerve Stimulation (taVNS) for Major Depressive Disorder: An Open Label Proof-of-Concept Trial

Despite recent advances in pharmacological treatments, Major Depressive Disorder (MDD) remains an incapacitating psychiatric condition with increasing prevalence and economic burden [1]. New therapeutical strategies such as vagus nerve stimulation (VNS) are being studied [2]. Different brain sites can be modulated by using electrical currents, which can theoretically restore balance to impaired circuits leading to clinical amelioration of symptoms. VNS involves the direct stimulation of the vagus nerve leading to further modulation of impaired brain areas related to psychiatric disorders [3,4]. Target stimulated areas include solitary tract nucleus, dorsal raphe, locus coeruleus, parabrachial area, amygdala, nucleus accumbent, hippocampus and the dorsolateral prefrontal cortex (DLPFC) [5]. Non-invasive VNS stimulation protocols have been assessed with promising results [6]. In fact, our group and others have recently proposed a hypothetically safer non-invasive approach for transcutaneously stimulating the vagus nerve in the ear, transcutaneous auricular VNS (taVNS) [7]. There are also methods for noninvasively stimulating the vagus nerve in the neck, or cervical region, called transcutaneous cervical VNS (tcVNS).We undertook this proofof-concept study to evaluate both the safety and potential clinical efficacy of this new experimental protocol with taVNS for treating patients with MDD. The present protocol had approval from institutional review board. Patients diagnosed with MDD according to the DSM-V criteria were recruited in an outpatient university hospital clinic. Symptom severity was assessed by the 17-itemHamilton Depression Rating Scale (HDRS). Exploratory analyses assessed depressive symptoms through the Beck Depression Inventory (BDI), anxiety symptoms through the Hamilton Anxiety Rating Scale (HAMA) and the Beck Anxiety Inventory (BAI), sleep quality through the Pittsburgh Sleep Quality Index (PSQI), and somatic symptoms through the Somatic Symptom Inventory (SSI) and the Somatoform Disorders Screening Instrument-7 days (SOMS-7). We also assessed cognitive functions with the Montreal Cognitive Assessment instrument (MoCA). Inclusion criteria were as follows: (1) 18to 59-year-old patients, (2) patients diagnosed with MDD following DSM-V criteria, (3) agreement to participate in the trial with written informed consent. Exclusion criteria were the following: (1) imminent need for psychiatric hospitalization, (2) any other [current or lifetime] psychiatric diagnosis, (3) neurologic or other severe diseases such as neoplastic syndromes and neurodegenerative and uncompensated chronic comorbidities, and (4) pregnancy. Clinical assessment was performed by a trained psychiatrist at baseline, at the last day of the stimulation protocol and one month after. The primary outcome was assessed by the mean difference in HDRS scores between baseline and the last day of stimulation. Participants were required to have at least four weeks without a change in psychiatric medication before the beginning of taVNS stimulation until the end of the one-month follow-up period. All patients underwent a 10-session taVNS protocol during a twoweek period. Electrical stimulationwas performed using the Ibramed Neurodyn II external neurostimulator to deliver electric current through the auricular branch of the vagus nerve at 120 Hz with a pulse wave duration of 250 μs for 30 minutes per day. The intensity was set at 12mA, which provoked a nonpainful mild paresthesia without muscle contraction for all patients. We performed the stimulation placing the electrodes bilaterally over the mastoid process area (anode to the left and cathode to the right), juxtaposed to the ear, near the tympanomastoid fissure (see Fig. 1) [8]. We used 15 cm2 auto-adhesive rubber electrodes to deliver the current. The present work was performed at the Interdisciplinary Center for Clinical Neuromodulation, Santa Casa School of Medical Sciences, São Paulo, Brazil. Figure 1. Anode positioning over the mastoid process area, juxtaposed to the ear. The cathode was positioned in the same way over the right mastoid process area.

Integrity of cognitive functions in trigeminal nerve stimulation trials in neuropsychiatry

It is common for both practitioners and patients to have concerns about the possible neurocognitive side effects of neuromodulation techniques and these may also be related to poor adherence.1 Electroconvulsive therapy (ECT) is currently considered the most effective treatment for severe depression. However, effects such as anterograde and retrograde amnesia and impairment of orientation, processing speed, attention, verbal fluency, and executive functions have been reported after ECT sessions.1 Clinical trials investigating neuropsychological outcomes after neuromodulation strategies therefore tend to focus on cognitive safety. Trigeminal nerve stimulation (TNS) is a transcutaneous neuromodulation technique based on the “bottom-up mechanism” in which alternating electric current is administered over the supraorbitary branch of the trigeminal nerve and stimuli propagate towards brain areas related to symptoms of depression and anxiety, modulating their activities. The efficacy of TNS for major depressive disorder has been studied and the results are interesting.2,3 However, investigations are still ongoing into safety issues related to TNS, such as compromise to skin integrity.4 We present an exploratory analysis of cognitive assessments conducted in clinical trials undertaken by our neuromodulation group. As part of clinical trials performed to investigate the efficacy of TNS for neuropsychiatric disorders such as depression, generalized anxiety, fibromyalgia, panic disorder, posttraumatic stress disorder5 and obsessivecompulsive disorder, 64 patients have been evaluated for cognitive function before and after a TNS protocol, using the Montreal Cognitive Assessment (MOCA). The TNS protocol used was as proposed by Shiozawa et al.3 and involves using an external neurostimulator to deliver an electric current with a frequency of 120 Hz and a pulse duration of 200 ms for 30 minutes. Intensity is Integridade das funções cognitivas em ensaios clínicos de estimulação do nervo trigêmeo em neuropsiquiatria

Effect of transcranial direct current stimulation (tDCS) over the prefrontal cortex combined with cognitive training for treating schizophrenia: a sham-controlled randomized clinical trial

Introduction: We report a transcranial direct current stimulation (tDCS) protocol over the dorsolateral prefrontal cortex (DLPFC) combined with cognitive training in schizophrenia. Method: We assessed psychotic symptoms in nine patients using the Positive and Negative Syndrome Scale (PANSS). All evaluations were scored at baseline, at the end of the intervention protocol, and during a 4-week follow-up. The tDCS protocol consisted of 10 consecutive sessions over 5-day periods. We placed the cathode over the right and the anode over the left DLPFC. For sham stimulation, we turned the device off after 60 seconds. Cognitive training consisted of the administration of N-back and sequence learning tasks. Results: We performed an analysis of covariance (ANCOVA) to adjust for the dependent variable PANSS, considering the interaction with baseline severity scores (p = 0.619). Mixed analysis of variance (ANOVA) showed no statistical significance between the groups regarding final PANSS scores. Conclusion: The results failed to demonstrate that the concomitant use of tDCS and cognitive training is effective to improve clinical outcomes in patients with schizophrenia. The present findings should be analyzed with care, considering the small sample size. Larger controlled trials on electric/cognitive stimulation should be produced in order to enhance therapeutic strategies in schizophrenia.

Effects of transcranial direct current stimulation on working memory and negative symptoms in schizophrenia: a phase II randomized sham-controlled trial

Background The lack of efficacy of pharmacological treatments for cognitive and negative symptoms in schizophrenia highlights the need for new interventions. We investigated the effects of tDCS on working memory and negative symptoms in patients with schizophrenia. Method Double-blinded, randomized, sham-controlled clinical trial, investigating the effects of 10 sessions of tDCS in schizophrenia subjects. Stimulation used 2 mA, for 20 min, with electrodes of 25 cm2 wrapped in cotton material soaked in saline solution. Anode was positioned over the left DLPFC and the cathode in the contralateral area. Twenty-four participants were assessed at baseline, after intervention and in a three-months follow-up. The primary outcome was the working memory score from MATRICS and the secondary outcome the negative score from PANSS. Data were analyzed using generalized estimating equations. Results We did not find group ∗ time interaction for the working memory (p = 0.720) score or any other cognitive variable (p > 0.05). We found a significant group ∗ time interaction for PANSS negative (p < 0.001, d = 0.23, CI.95 = −0.59–1.02), general (p = 0.011) and total scores (p < 0.001). Exploratory analysis of PANSS 5 factors suggests tDCS effect on PANSS negative (p = 0.012), cognitive (p = 0.016) and depression factors (p = 0.029). Conclusion The results from this trial highlight the therapeutic effects of tDCS for treatment of persistent symptoms in schizophrenia, with reduction of negative symptoms. We were not able to confirm the superiority of active tDCS over sham to improve working memory performance. Larger sample size studies are needed to confirm these findings.

Neuropsychological Aspects Observed in a Nuclear Plant Simulator and Its Relation to Human Reliability Analysis

This paper will discuss preliminary results of an evaluation methodology for the analysis and quantification of errors in manual (human) operation by training cognitive parameters and skill levels in the complex control system operation based on Neuropsychology and Psychophysiology approaches. The research was conducted using a game (nuclear power plant simulator) that simulates concepts of operation of a nuclear plant with a split sample evaluating aspects of learning and knowledge in the nuclear context. Operators were monitored using biomarkers (ECG, EEG, GSR, face detection and eye tracking) and the results were analyzed by statistical multivariate techniques. The experiments aimed at observing state change situations such as shutdowns and planned matches, incidents assumptions and ordinary features of operation. The preliminary findings of this research effort indicate that neuropsychological aspects can contribute to improve the available human reliability techniques by making them more realistic both in the context of quantitative approaches for regulatory purposes as well as in reducing the incidence of human error.