Home-Use Transcranial Direct Current Stimulation for the Treatment of a Major Depressive Episode: A Randomized Clinical Trial.

Importance: Transcranial direct current stimulation (tDCS) is moderately effective for depression when applied by trained staff. It is not known whether self-applied tDCS, combined or not with a digital psychological intervention, is also effective. Objective: To determine whether fully unsupervised home-use tDCS, combined with a digital psychological intervention or digital placebo, is effective for a major depressive episode. Design, Setting, and Participants: This was a double-blinded, sham-controlled, randomized clinical trial with 3 arms: (1) home-use tDCS plus a digital psychological intervention (double active); (2) home-use tDCS plus digital placebo (tDCS only), and (3) sham home-use tDCS plus digital placebo (double sham). The study was conducted between April 2021 and October 2022 at participants' homes and at Instituto de Psiquiatria do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil. Included participants were aged 18 to 59 years with major depression and a Hamilton Depression Rating Scale, 17-item version (HDRS-17), score above 16, a minimum of 8 years of education, and access to a smartphone and internet at home. Exclusion criteria were other psychiatric disorders, except for anxiety; neurologic or clinical disorders; and tDCS contraindications. Interventions: tDCS was administered in 2-mA, 30-minute prefrontal sessions for 15 consecutive weekdays (1-mA, 90-second duration for sham) and twice-weekly sessions for 3 weeks. The digital intervention consisted of 46 sessions based on behavioral therapy. Digital placebo was internet browsing. Main Outcomes and Measures: Change in HDRS-17 score at week 6. Results: Of 837 volunteers screened, 210 participants were enrolled (180 [86%] female; mean [SD] age, 38.9 [9.3] years) and allocated to double active (n = 64), tDCS only (n = 73), or double sham (n = 73). Of the 210 participants enrolled, 199 finished the trial. Linear mixed-effects models did not reveal statistically significant group differences in treatment by time interactions for HDRS-17 scores, and the estimated effect sizes between groups were as follows: double active vs tDCS only (Cohen d, 0.05; 95% CI, -0.48 to 0.58; P = .86), double active vs double sham (Cohen d, -0.20; 95% CI, -0.73 to 0.34; P = .47), and tDCS only vs double sham (Cohen d, -0.25; 95% CI, -0.76 to 0.27; P = .35). Skin redness and heat or burning sensations were more frequent in the double active and tDCS only groups. One nonfatal suicide attempt occurred in the tDCS only group. Conclusions and Relevance: Unsupervised home-use tDCS combined with a digital psychological intervention or digital placebo was not found to be superior to sham for treatment of a major depressive episode in this trial. Trial Registration: ClinicalTrials.gov Identifier: NCT04889976.

Incidence of Suicidal Ideation in a Civil Servants Cohort During the COVID-19 Pandemic in Brazil: Insights from the ELSA-Brasil Study.

OBJECTIVE: This study investigated the incidence of suicidal ideation and its associated risk factors in the São Paulo state of ELSA-Brasil cohort during the COVID-19 pandemic. METHODS: During a pre-pandemic ELSA-Brasil onsite assessment in 2016-2018 (wave 3) and a pandemic online assessment in May-July 2020 (wave COVID), we assessed suicidal ideation using the Clinical Interview Scheduled-Revised (CIS-R). Single and multi predictor logistic regressions were performed using sociodemographic characteristics, household finance impact during pandemic, presence of previous chronic diseases, alcohol abuse, adverse childhood experiences (ACE), living alone, and previous CMD as predictors. Suicidal ideation incidence was used as outcome. RESULTS: Out of 4191 participants of wave 3, 2117 (50.5%) answered wave COVID. There was a threefold increase in suicide ideation, from 34 (1.8%) to 104 (5.6%).In multiple predictor models, we found that previous CMD (OR 7.17; 95% CI 4.43 - 11.58) and ACE (OR 1.72; 95% CI 1.09 - 2.72) increased the odds of incident suicidal ideation. The sociodemographic predictors female sex, younger age and low income were significant risk factors only in the single predictor model. Conclusions These findings underscore the importance of monitoring and supporting individuals who suffered ACE and have a history of mental health disorders. This is especially critical in times of heightened societal stress, such as the COVID-19 pandemic. CONCLUSIONS: These findings underscore the importance of monitoring and supporting individuals who suffered ACE and have a history of mental health disorders. This is especially critical in times of heightened societal stress, such as the COVID-19 pandemic.

Trajectories of common mental disorders symptoms before and during the COVID-19 pandemic: findings from the ELSA-Brasil COVID-19 Mental Health Cohort.

AIM: Evidence indicates most people were resilient to the impact of the COVID-19 pandemic on mental health. However, evidence also suggests the pandemic effect on mental health may be heterogeneous. Therefore, we aimed to identify groups of trajectories of common mental disorders' (CMD) symptoms assessed before (2017-19) and during the COVID-19 pandemic (2020-2021), and to investigate predictors of trajectories. METHODS: We assessed 2,705 participants of the ELSA-Brasil COVID-19 Mental Health Cohort study who reported Clinical Interview Scheduled-Revised (CIS-R) data in 2017-19 and Depression Anxiety Stress Scale-21 (DASS-21) data in May-July 2020, July-September 2020, October-December 2020, and April-June 2021. We used an equi-percentile approach to link the CIS-R total score in 2017-19 with the DASS-21 total score. Group-based trajectory modeling was used to identify CMD trajectories and adjusted multinomial logistic regression was used to investigate predictors of trajectories. RESULTS: Six groups of CMD symptoms trajectories were identified: low symptoms (17.6%), low-decreasing symptoms (13.7%), low-increasing symptoms (23.9%), moderate-decreasing symptoms (16.8%), low-increasing symptoms (23.3%), severe-decreasing symptoms (4.7%). The severe-decreasing trajectory was characterized by age < 60 years, female sex, low family income, sedentary behavior, previous mental disorders, and the experience of adverse events in life. LIMITATIONS: Pre-pandemic characteristics were associated with lack of response to assessments. Our occupational cohort sample is not representative. CONCLUSION: More than half of the sample presented low levels of CMD symptoms. Predictors of trajectories could be used to detect individuals at-risk for presenting CMD symptoms in the context of global adverse events.

A study protocol for an ongoing multi-arm, randomized, double-blind, sham-controlled clinical trial with digital features, using portable transcranial electrical stimulation and internet-based behavioral therapy for major depression disorders: The PSYLECT study.

BACKGROUND: Transcranial electrical stimulation (tES) is considered effective and safe for depression, albeit modestly, and prone to logistical burdens when performed in external facilities. Investigation of portable tES (ptES), and potentiation of ptES with remote psychological interventions have shown positive, but preliminary, results. RESEARCH DESIGN: We report the rationale and design of an ongoing multi-arm, randomized, double-blind, sham-controlled clinical trial with digital features, using ptES and internet-based behavioral therapy (iBT) for major depressive disorder (MDD) (NCT04889976). METHODS: We will evaluate the efficacy, safety, tolerability and usability of (1) active ptES + active iBT ('double-active'), (2) active ptES + sham iBT ('ptES-only'), and (3) sham ptES + sham iBT ('double-sham'), in adults with MDD, with a Hamilton Depression Rating Scale - 17 item version (HDRS-17) score ≥ 17 at baseline, during 6 weeks. Antidepressants are allowed in stable doses during the trial. RESULTS: We primarily co-hypothesize changes in HDRS-17 will be greater in (1) 'double-active' compared to 'ptES-only,' (2) 'double-active' compared to 'double-sham,' and (3) 'ptES-only' compared to 'double-sham.' We aim to enroll 210 patients (70 per arm). CONCLUSIONS: Our results should offer new insights regarding the efficacy and scalability of combined ptES and iBT for MDD, in digital mental health.

Effects of combining retrieval practice and tDCS over long-term memory: A randomized controlled trial.

The ability to retain new information is important in daily life. In particular, two techniques have shown promise for improving long-term retention: retrieval practice (RP), which consists of actively retrieving information from long-term memory to make it more accessible in the future; and transcranial direct current stimulation (tDCS), which consists of non-invasive brain stimulation that modulates cognitive processes by increasing and decreasing neuronal excitability. Previous studies have implicated the left dorsolateral prefrontal cortex (l-dlPFC) in memory encoding and memory organization. We examined whether RP associated with a single 20-min tDCS session over the l-dlPFC could improve long-term memory retention. Participants (N = 119) repeatedly studied a list of related words either via RP or via restudy, while undergoing either anodal or sham stimulation. Participants returned 2 days later for a free-recall test. Results showed that the RP group outperformed the restudy group in all measures, regardless of stimulation type. Also, recall organization was higher in the RP group than in the restudy group. The data support previous findings and indicate that RP may enhance performance by improving the organization of the to-be-remembered list items.

The Effects of Transcranial Direct Current Stimulation in Obsessive-Compulsive Disorder Symptoms: A Meta-Analysis and Integrated Electric Fields Modeling Analysis.

Transcranial direct current stimulation (tDCS) has been showing promising effects for the treatment of obsessive-compulsive disorder (OCD), but there is still no conclusion on its efficacy for this disorder. We performed a systematic review and meta-analysis of trials using tDCS for OCD and a computer modeling analysis to evaluate the electric field (EF) strengths of different electrode assemblies in brain regions of interest (ROIs) (PROSPERO-42021262465). PubMed/MEDLINE, Embase, Cochrane Library and Web of Science databases were searched from inception to 25 September 2022. Randomized controlled trials (RCTs) and open-label studies were included. The primary aim was the effect size (Hedges' g) of continuous outcomes and potential moderators of response. For EF modeling, SimNIBS software was used. Four RCTs and four open-label trials were included (n = 241). Results revealed a large effect of tDCS in the endpoint, but no significant effect between active and sham protocols. No predictor of response was found. EF analysis revealed that montages using the main electrode over the (pre)supplementary motor area with an extracephalic reference electrode might lead to stronger EFs in the predefined ROIs. Our results revealed that tDCS might be a promising intervention to treat OCD; however, larger studies are warranted.

Terapia de produção audiovisual associada a estimulação por corrente contínua melhora nomeação em paciente com afasia de Broca e doença de Parkinson / Audiovisual production therapy associated with transcranial current stimulation improves naming in a patient with Broca's aphasia and Parkinson's disease

RESUMO A doença de Parkinson (DP) é uma doença neurodegenerativa, caracterizada por disfunções motoras e não motoras. Pacientes com DP também podem apresentar problemas de linguagem, incluindo deficit em tarefas de nomeação. Dificuldade em tarefas de nomeação é uma característica importante da afasia de Broca, transtorno de linguagem associado a lesões pós-acidente vascular cerebral (AVC) no córtex pré-frontal inferior esquerdo (área de Broca). Aqui, apresenta-se o caso de um paciente de 79 anos diagnosticado com DP (estágio 4 na escala de Hoehn e Yahr) e afasia crônica não fluente pós-AVC, com deficit de nomeação severos. O paciente foi tratado com uma nova combinação de terapia audiovisual de produção e estimulação transcraniana por corrente contínua (ETCC), técnica neuromodulatória não invasiva, que tem sido cada vez mais adotada para potencializar terapias fonoaudiológicas. ETCC anodal (2 mA) foi aplicada sobre o córtex pré-frontal inferior esquerdo (F7 no sistema 10/20), durante nove sessões de 20 minutos, ao longo de duas semanas, enquanto o paciente tentava nomear imagens de objetos comuns com o auxílio de vídeos curtos mostrando uma boca articulando os sons do nome do objeto (pista audiovisual). Observou-se aumento significativo nos escores de nomeação entre o pré e o pós-tratamento, tanto para imagens treinadas, quanto para não treinadas, mas fonemicamente similares (generalização). Os resultados apresentaram indícios iniciais de que terapia audiovisual de produção associada à ETCC anodal sobre a área de Broca pode representar uma alternativa viável para pacientes com deficits de nomeação severos.

ABSTRACT Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and nonmotor symptoms. PD patients may present language problems, including deficits in confrontation naming. Naming deficits are also an important feature of Broca's aphasia, a condition associated with post-stroke damage to the left inferior prefrontal cortex (Broca's area). We present the case of a 79-year old, male patient diagnosed with both PD (stage 4 in Hoehn and Yahr's scale) and chronic post-stroke, non-fluent aphasia. The patient, with particularly severe naming deficits, was treated with a novel combination of audiovisual production therapy and transcranial direct current stimulation (tDCS), a noninvasive neuromodulatory technique that has been increasingly used to potentiate speech therapy. Anodal tDCS (2 mA) was applied to the left inferior prefrontal cortex (F7 in the 10/20 system) in nine 20-min sessions over two weeks while the patient tried to name pictures of common objects aided by short videos of an articulating mouth (audiovisual cue). We found significant pre- to post-training naming improvement for treated items and for untreated, phonemically similar items (generalization). The results provide initial indication that audiovisual production therapy combined with anodal tDCS over Broca's area may represent a viable treatment alternative for patients with severe naming deficits.

Acute offline transcranial direct current stimulation does not change pain or anxiety produced by the cold pressor test.

Transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) has an antalgic effect on acute experimental pain in healthy volunteers. Many published studies have used online stimulation (i.e., tDCS performed during painful stimulation). On the other hand, daily tDCS sessions have been proposed as a therapy for chronic pain (offline tDCS). In such cases, the therapeutic potential depends on the possible aftereffects of each tDCS session. We set out to investigate whether a single tDCS session before application of a classical experimental pain paradigm (the Cold Pressor Test, CPT) would be capable of modulating physiological measures of anxiety as well as pain perception. tDCS was applied to 30 healthy volunteers, 18-28 years old (mean 18.5), with the anode positioned over either the left M1 or the left dorsolateral prefrontal cortex (l-DLPFC), which has been linked to the affective aspects of experienced pain, including anxiety. All volunteers underwent the CPT procedure before and after a tDCS session. Real 2 mA tDCS sessions for 20 min were compared to sham stimulations. No significant difference was found for any variable after real tDCS sessions when compared to the sham stimulations. This result suggests that effective offline tDCS for chronic pain might have different mechanisms of action. Cumulative effects, functional targeting and the unintended simultaneous stimulation of both M1 and the l-DLPFC are likely responsible for the therapeutic effects of tDCS sessions in the clinical setting.

Retrieval Practice in Memory- and Language-Impaired Populations: A Systematic Review.

OBJECTIVE: Neurological conditions, such as multiple sclerosis and stroke, may impair memory and language. A technique called retrieval practice (RP) may improve memory and language outcomes in such clinical populations. The RP effect refers to the finding that retrieving information from memory leads to better long-term retention than restudying the same information. Although the benefits of RP have been repeatedly observed in healthy populations, less is known about its potential applications in cognitive rehabilitation in clinical populations. Here we review the RP literature in populations with acquired memory and language impairments. METHOD: Systematic searches for studies published before January 2020 were conducted on Elsevier, PsycARTICLES, PsycINFO, Pubmed, Web of Science, and Wiley Online Library, with the terms "retrieval practice"/"testing effect" and "cognitive rehabilitation". In addition, backward and forward snowballing were used to allow the identification of important publications missed by the initial search. Studies were included if they were peer-reviewed, empirical work in which memory or language outcome measures were compared between an RP condition and a re-exposure-control condition in patients with acquired memory or language impairments. RESULTS: Sixteen articles fulfilled the inclusion criteria. Studies from memory-impaired samples were relatively homogeneous with respect to experimental protocols and materials and favored RP over control conditions. The results were mostly positive despite short retention intervals and predominantly single-session designs. Similarly, studies from language-impaired samples focused on naming impairments in patients with aphasia and also favored RP over name repetition. CONCLUSION: The results indicate that RP is a viable technique for cognitive rehabilitation.