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Traumatic brain injury (TBI) remains a global health problem with cognitive impairments that can affect an individual’s life. Although there is still no effective treatment for TBI sequelae, virtual reality (VR) technology shows promising results as a training tool to improve cognitive functions. Nonetheless, using a head-mounted display (HMD) device can induce cybersickness. Objective. To assess the feasibility of immersive VR cognitive training on EF and provide insights for a definitive trial. We aimed to assess the tolerability of TBI patients after prolonged use of a HMD. Also, as an exploratory analysis, we evaluated changes in cognition, including executive function, memory, and processing speed after the intervention. Methods. A prospective, single-arm, quasi-experimental study was performed to analyze the feasibility of twelve 20-min sessions of immersive VR over four weeks in patients with sustained TBI. Neuropsychological assessment was applied at baseline (T1), post-intervention (T2), and a three-months follow-up (T3). The Simulator Sickness Questionnaire (SSQ) was administered at the end of each session to evaluate the safety of the intervention. Results. Thirteen participants of mean age 34.86 (11.12), with moderate to severe TBI and average of 305.23 (51.23) days post-trauma were included. Patients showed improvements in EF between T1 and T3 (p = 0.02) and low scores in the SSQ (mean score = 4.33, SD = 4.06). Conclusions. The present VR intervention showed to be feasible and safe for patients with TBI to use a HMD. We also observed positive effects on EF and future studies should consider a home-based approach.

Diffusion tensor imaging (DTI) parameters in the corpus callosum have been suggested to be a biomarker for prognostic outcomes in individuals with diffuse axonal injury (DAI). However, differences between the DTI parameters on moderate and severe trauma in DAI over time are still unclear. A secondary goal was to study the association between the changes in the DTI parameters, anxiety, and depressive scores in DAI over time. Twenty subjects were recruited from a neurological outpatient clinic and evaluated at 2, 6, and 12 months after the brain injury and compared to matched age and sex healthy controls regarding the DTI parameters in the corpus callosum. State-Trace Anxiety Inventory and Beck Depression Inventory were used to assess psychiatric outcomes in the TBI group over time. Differences were observed in the fractional anisotropy and mean diffusivity of the genu, body, and splenium of the corpus callosum between DAI and controls (p

IntroductionDeficits in episodic memory following traumatic brain injury (TBI) are common and affect independence in activities of daily living. Transcranial direct current stimulation (tDCS) and concurrent cognitive training may contribute to improve episodic memory in patients with TBI. Although previous studies have shown the potential of tDCS to improve cognition, the benefits of the tDCS applied simultaneously to cognitive training in participants with neurological disorders are inconsistent. This study aims to (1) investigate whether active tDCS combined with computer-assisted cognitive training enhances episodic memory compared with sham tDCS; (2) compare the differences between active tDCS applied over the left dorsolateral prefrontal cortex (lDLPFC) and bilateral temporal cortex (BTC) on episodic memory and; (3) investigate inter and intragroup changes on cortical activity measured by quantitative electroencephalogram (qEEG).Methods and analysisA randomised, parallel-group, double-blind placebo-controlled study is conducted. Thirty-six participants with chronic, moderate and severe closed TBI are being recruited and randomised into three groups (1:1:1) based on the placement of tDCS sponges and electrode activation (active or sham). TDCS is applied for 10 consecutive days for 20 min, combined with a computer-based cognitive training. Cognitive scores and qEEG are collected at baseline, on the last day of the stimulation session, and 3 months after the last tDCS session. We hypothesise that (1) the active tDCS group will improve episodic memory scores compared with the sham group; (2) differences on episodic memory scores will be shown between active BTC and lDLPFC and; (3) there will be significant delta reduction and an increase in alpha waves close to the location of the active electrodes compared with the sham group.Ethics and disseminationThis study was approved by Hospital das Clínicas, University of São Paulo Ethical Institutional Review Border (CAAE: 87954518.0.0000.0068).Trial registration numberNCT04540783.

Anxiety is currently one of the main mood changes and can impair the quality of life of the individual when associated with other neurological or psychiatric disorders. Neuromodulation has been highlighted as a form of treatment of several pathologies, including those involving anxiety symptoms. Among the neuromodulatory options with the potential to improve mood changes, we highlight repetitive transcranial magnetic stimulation (rTMS). rTMS is a viable therapeutical option for neuropsychiatric dysfunctions of high prevalence and is important for the understanding of pathological and neuropsychological adaptation processes. Even with this potential, and high relevance of intervention, we observe the scarcity of literature that covers this subject. The objective of this study was to carry out a survey of the current literature, using scientific databases for the last five years. We found 32 studies reporting the effects of rTMS on anxiety, 7 on anxiety disorders and 25 on anxiety symptoms as comorbidities of neurological or psychiatric disorders. This survey suggests the need for further studies using TMS for anxiety in order to seek strategies that minimize these anxiety effects on the quality of life of the victims of this disorder.

ObjectiveTo determine whether high-frequency repetitive transcranial magnetic stimulation (rTMS) improves cognition in patients with severe traumatic brain injury.MethodsA single-center, randomized, double-blind, placebo-controlled study of rTMS was conducted in patients aged 18–60 years with chronic (>12 months postinjury) diffuse axonal injury (DAI). Patients were randomized to either a sham or real group in a 1:1 ratio. A 10-session rTMS protocol was used with 10-Hz stimulation over the left dorsolateral prefrontal cortex (DLPFC). Neuropsychological assessments were performed at 3 time points: at baseline, after the 10th rTMS session, and 90 days after intervention. The primary outcome was change in executive function evaluated using the Trail Making Test Part B.ResultsThirty patients with chronic DAI met the study criteria. Between-group comparisons of performance on TMT Part B at baseline and after the 10th rTMS session did not differ between groups (p = 0.680 and p = 0.341, respectively). No significant differences were observed on other neuropsychological tests. No differences in adverse events between treatment groups were observed.ConclusionsCognitive function in individuals with chronic DAI is not improved by high-frequency rTMS over the left DLPFC, though it appears safe and well-tolerated in this population.ClinicalTrials.gov identifierNCT02167971.Classification of evidenceThis study provides Class II evidence that for individuals with chronic DAI, high-frequency rTMS over the left DLPFC does not significantly improve cognition.

Diffusion tensor imaging (DTI) parameters in the corpus callosum have been suggested to be a biomarker for prognostic outcomes in individuals with diffuse axonal injury (DAI). However, differences between the DTI parameters on moderate and severe trauma in DAI over time are still unclear. A secondary goal was to study the association between the changes in the DTI parameters, anxiety, and depressive scores in DAI over time.Twenty subjects were recruited from a neurological outpatient clinic and evaluated at 2, 6, and 12 months after the brain injury and compared to matched age and sex healthy controls regarding the DTI parameters in the corpus callosum. State-Trace Anxiety Inventory and Beck Depression Inventory were used to assess psychiatric outcomes in the TBI group over time.Differences were observed in the fractional anisotropy and mean diffusivity of the genu, body, and splenium of the corpus callosum between DAI and controls (p 0.02). Differences in both parameters in the genu of the corpus callosum were also detected between patients with moderate and severe DAI (p 0.05). There was an increase in the mean diffusivity values and the fractional anisotropy decrease in the DAI group over time (p 0.02). There was no significant correlation between changes in the fractional anisotropy and mean diffusivity across the study and psychiatric outcomes in DAI.DTI parameters, specifically the mean diffusivity in the corpus callosum, may provide reliable characterization and quantification of differences determined by the brain injury severity. No correlation was observed with DAI parameters and the psychiatric outcome scores.

Objective: The goal is to evaluate longitudinally with diffusion tensor imaging (DTI) the integrity of cerebral white matter in patients with moderate and severe DAI and to correlate the DTI findings with cognitive deficits.Methods: Patients with DAI (n = 20) were scanned at three timepoints (2, 6 and 12 months) after trauma. A healthy control group (n = 20) was evaluated once with the same high-field MRI scanner. The corpus callosum (CC) and the bilateral superior longitudinal fascicles (SLFs) were assessed by deterministic tractography with ExploreDTI. A neuropschychological evaluation was also performed.Results: The CC and both SLFs demonstrated various microstructural abnormalities in between-groups comparisons. All DTI parameters demonstrated changes across time in the body of the CC, while FA (fractional anisotropy) increases were seen on both SLFs. In the splenium of the CC, progressive changes in the mean diffusivity (MD) and axial diffusivity (AD) were also observed. There was an improvement in attention and memory along time. Remarkably, DTI parameters demonstrated several correlations with the cognitive domains.Conclusions: Our findings suggest that microstructural changes in the white matter are dynamic and may be detectable by DTI throughout the first year after trauma. Likewise, patients also demonstrated improvement in some cognitive skills.

X-linked Dystonia-Parkinsonism (XDP) is a progressive, disabling disease characterized by the devastating impairment of bulbar function, including speech and swallowing. Despite these detrimental impacts, bulbar impairments in this population are not well characterized.To identify impairments in the bulbar system measured by oromotor performance in individuals with XDP relative to healthy controls. Secondarily, to detect diagnostic bulbar markers that are sensitive and specific to the initial years of XDP.This case-control study included 25 healthy controls and 30 participants with XDP, divided into two subgroups based on the median of their disease length. Multiple clinical and instrumental oromotor tasks and measures were used to evaluate bulbar motor function.Differences were found between both the subgroups with XDP and healthy controls on almost all measures, including maximum performance tasks such as tongue strength, alternating motion rate (AMR), and sequential motion rate (SMR) (p 0.05). Differences were found between the XDP subgroups and the control group for the percentage of pause time during the speech, a rating of speech severity, and a swallowing task (ps 0.05). Scores on self-reported questionnaires, tongue strength, the number of repetitions produced during an AMR, percent pause, and speech severity demonstrated good sensitivity and specificity to differentiate the initial years of XDP onset from healthy controls.Our findings revealed impairments across bulbar functions in participants within the first 7 years of the XDP onset. Highly sensitive and specific bulbar impairment measures were detected in instrumental and self-reported measures that are fundamental for monitoring disease.

Background Chronic hepatitis C virus (HCV) infection is associated with impairment of cognitive function and mood disorders. Our aim was to evaluate the impact of sustained virological response (SVR) on cognitive function and mood disorders. Method A prospective exploratory one arm study was conducted. Adult clinically compensated HVC patients were consecutively recruited before treatment with interferon and ribavirin for 24 to 48 weeks, according to HCV genotype. Clinical, neurocognitive and mood assessments using the PRIME-MD and BDI instruments were performed at baseline, right after half of the expected treatment has been reached and 6 months after the end of antiviral treatment. Exclusion criteria were the use of illicit psychotropic substances, mental confusion, hepatic encephalopathy, hepatocellular carcinoma, severe anemia, untreated hypothyroidism, Addison syndrome and major depression before treatment. Results Thirty six patients were enrolled and 21 completed HCV treatment (n = 16 with SVR and n = 5 without). Regardless of the viral clearance at the end of treatment, there was a significant improvement in the immediate verbal episodic memory (p = 0.010), delayed verbal episodic memory (p = 0.007), selective attention (p

Hypnosis is a valuable tool in the management of patients who undergo surgical procedures in the maxillofacial complex, particularly in reducing and eliminating pain during surgery and aiding patients who have dental fear and are allergic to anesthesia. This case report demonstrates the efficacy of hypnosis in mitigating anxiety, bleeding, and pain during dental surgery without anesthesia during implant placement of tooth 14, the upper left first molar.

Traumatic brain injury (TBI) is a major public health problem in Western countries. A TBI brings many negative consequences, including behavioral and cognitive changes, which affect social adjustment and the performance of functional activities. Cognitive evaluation after TBI is a complex issue in what pertains to definition of the most appropriate questionnaires for clinical use in a comprehensive analysis of the condition of the patient. In this paper, we described a critical review of the main cognitive assessment tests currently used in clinical and research settings in patients with TBI.

Long-term trials are key to understanding chronic symptoms such as pain and itch. However, challenges such as high attrition rates and poor recruitment are common when conducting research. The aim of this work was to explore these issues within a long-term randomized control trial using transcranial direct current stimulation to treat pain and itch. This parallel double blinded, placebo-controlled randomized trial was comprised of 15 transcranial direct current stimulation visits and 7 follow-up visits. Participants were over the age of 18, had a burn injury that occurred at least 3 weeks before enrollment, and reported having pain and/or itch that was moderate to severe in intensity. A total of 31 subjects were randomized into either an active or sham transcranial direct current stimulation groups. There were no significant differences between the groups in terms of age, race, education, baseline depression, or anxiety. The median dropout time was at visit 19 (visit 16 [SE = 1.98] for the sham group and visit 19 [SE = 1.98] for the active group). Analysis showed no differences in the dropout rate between groups [χ2(1) = 0.003, P = .954]. The dropout rate was 46.7% for the sham group and 43.8% for the active group. Overall, 45.2% of the subjects dropped out of the trial. Long-term clinical trials are an essential part of evaluating interventions for symptoms such as chronic pain and itch. However, as seen in this trial, long-term studies in the burn population often face recruitment and adherence challenges.

Diffuse axonal injury (DAI) induces a long-term process of brain atrophy and cognitive deficits. The goal of this study was to determine whether there are correlations between brain volume loss, microhaemorrhage load (MHL) and neuropsychological performance during the first year after DAI.Twenty-four patients with moderate or severe DAI were evaluated at 2, 6 and 12 months post-injury. MHL was evaluated at 3 months, and brain volumetry was evaluated at 3, 6 and 12 months. The trail making test (TMT) was used to evaluate executive function (EF), and the Hopkins verbal learning test (HVLT) was used to evaluate episodic verbal memory (EVM) at 6 and 12 months.There were significant white matter volume (WMV), subcortical grey matter volume and total brain volume (TBV) reductions during the study period (p 0.05). MHL was correlated only with WMV reduction. EF and EVM were not correlated with MHL but were, in part, correlated with WMV and TBV reductions.Our findings suggest that MHL may be a predictor of WMV reduction but cannot predict EF or EVM in DAI. Brain atrophy progresses over time, but patients showed better EF and EVM in some of the tests, which could be due to neuroplasticity.

Background Photobiomodulation describes the use of red or near-infrared light to stimulate or regenerate tissue. It was discovered that near-infrared wavelengths (800–900 nm) and red (600 nm) light-emitting diodes (LED) are able to penetrate through the scalp and skull and have the potential to improve the subnormal cellular activity of compromised brain tissue. Different experimental and clinical studies were performed to test LED therapy for traumatic brain injury (TBI) with promising results. One of the proposals of this present study is to develop different approaches to maximize the positive effects of this therapy and improve the quality of life of TBI patients. Methods/design This is a double-blinded, randomized, controlled trial of patients with diffuse axonal injury (DAI) due to a severe TBI in an acute stage (less than 8 h). Thirty two patients will be randomized to active coil helmet and inactive coil (sham) groups in a 1:1 ratio. The protocol includes 18 sessions of transcranial LED stimulation (627 nm, 70 mW/cm2, 10 J/cm2) at four points of the frontal and parietal regions for 30 s each, totaling 120 s, three times per week for 6 weeks, lasting 30 min. Patients will be evaluated with the Glasgow Outcome Scale Extended (GOSE) before stimulation and 1, 3, and 6 months after the first stimulation. The study hypotheses are as follows: (1) transcranial LED therapy (TCLT) will improve the cognitive function of DAI patients and (2) TCLT will promote beneficial hemodynamic changes in cerebral circulation. Discussion This study evaluates early and delayed effects of TCLT on the cognitive rehabilitation for DAI following severe acute TBI. There is a paucity of studies regarding the use of this therapy for cognitive improvement in TBI. There are some experimental studies and case series presenting interesting results for TBI cognitive improvement but no clinical trials. Trial registration ClinicalTrials.gov, NCT03281759. Registered on 13 September 2017. Electronic supplementary material The online version of this article (10.1186/s13063-018-2632-5) contains supplementary material, which is available to authorized users.

Background: Mild traumatic brain injury (MTBI) represents 70-80% of all treated brain injuries. A considerable proportion of MTBI patients experience post-concussion symptoms for a prolonged period after MTBI, and these symptoms are diagnosed as persistent post-concussion syndrome (PPCS). PPCS is defined as a range of physical, cognitive and emotional symptoms. However, memory and executive dysfunction seems to be one of the most debilitating symptoms. Recently, non-invasive brain stimulation has been studied as a potential treatment method for traumatic brain injury (TBI) patients. Therefore, our primary goal is to verify the effects of TDCS in patients with PPCS who demonstrate cognitive deficits in long-term episodic memory, working memory and executive function following MTBI. Methods/design: This is a randomized crossover trial of patients with a history of MTBI with cognitive deficits in memory and executive function. Thirty adult patients will be randomized in a crossover manner to receive three weekly sessions of anodal tDCS (2mA) at left dorsolateral prefrontal cortex, left temporal cortex and sham stimulation that will be performed at 7-day intervals (washout period). The clinical diagnosis of PPCS will be determined using the Rivermead Post Concussion Symptoms Questionnaire. Patients who meet the inclusion criteria will be assessed with a neuropsychological evaluation. A new battery of computerized neuropsychological tests will be performed before and immediately after each stimulation. Statistical analysis will be performed to determine trends of cognitive improvement. Discussion: There are paucity of studies regarding the use of TDCS in TBI patients and, although recent results showed controversial data regarding the effects of TDCS in such patients, we will address specifically patients with PPCS and MTBI, and no brain abnormalities on CT scan other than subarachnoid hemorrhage. Moreover, due to the missing information on literature regarding the best brain region to be studied we will evaluate two different regions to find immediate effects of TDCS on memory and executive dysfunction. Ethics and dissemination: Ethics approval has been obtained from the Ethics Committee for review of research projects, Hospital das Clinicas, University of Sao Paulo (CAPPesq 612.643/14).

Neuropsychological and psychiatric disorders represent a major concern and cause of disabilities after the trauma, contributing to worse recovery after traumatic brain injury (TBI). However, the lack of well-defined parameters to evaluate patient’s psychiatric disorders leads to a wide range of diagnoses and symptoms. The aim of this study was to perform a review of literature in order to gather data of the most common scales and inventories used to assess and diagnose depression, anxiety, and posttraumatic stress disorder (PTSD) after TBI. We conducted a literature search via MEDLINE, PubMed, and Web of Science. We included reviews, systematic reviews, and meta-analysis studies, and we used the following keywords: “traumatic brain injury OR TBI,” “depression OR depressive disorder,” “anxiety,” and “posttraumatic stress disorder OR PTSD.” From 610 titles, a total of 68 systematic reviews or meta-analysis were included in the section “Results” of this review: depression (n = 32), anxiety (n = 9), and PTSD (n = 27). Depression after TBI is a more established condition, with more homogeneous studies. Anxiety and PTSD disorders have been studied in a heterogeneous way, usually as comorbidity with other psychiatric disorders. Some scales and inventories designed for the general community may not be appropriate for patients with TBI.

Ana Luiza Zaninotto,1 Tatiana Saito Paiva,2 Marcia André,2 Beatriz Silva Mattos,2 Wellingson Silva Paiva3 1Division of Psychology, Clinics Hospital at University of São Paulo Medical School, 2Department of Surgery, Prosthesis, and Maxillofacial Trauma, University of Sao Paulo Dentistry School, 3Division of Neurological Surgery, Department of Neurology, University of São Paulo Medical School, São Paulo, BrazilRecently, we read publications relating to helping students to improve their scientific thinking and writing;1,2 in which Sørensen wrote a brilliant paper entitled “I-determinants for successful PhD or postdoctoral outcome”.3 There is a new world in clinical and experimental research with many challenges for training new researchers. There is notable intensification of the International Scientific Cooperation, requiring more systematic programs for PhD students and research fellow training. In this paper, the author describes his extensive experience relating on how to identify the characteristics of PhD students and postdoctoral fellows that can successfully perform the training program and became an independent researcher.View original paper by Sørensen.

Traumatic brain injury (TBI) remains the main cause of disability and a major public health problem worldwide. This review focuses on the neurophysiology of TBI, and the rationale and current state of evidence of clinical application of brain stimulation to promote TBI recovery, particularly on consciousness, cognitive function, motor impairments, and psychiatric conditions. We discuss the mechanisms of different brain stimulation techniques including major noninvasive and invasive stimulations. Thus far, most noninvasive brain stimu­ lation interventions have been nontargeted and focused on the chronic phase of recovery after TBI. In the acute stages, there is limited available evidence of the efficacy and safety of brain stimulation to improve functional outcomes. Comparing the studies across different techniques, transcranial direct current stimulation is the intervention that currently has the higher number of properly designed clinical trials, though total number is still small. We recognize the need for larger studies with target neuroplasticity modulation to fully explore the benefits of brain stimulation to effect TBI recovery during different stages of recovery.

Ana Luiza Zaninotto,1 Vinícius Monteiro de Paula Guirado,2 Beatriz Baldivia,1 Monica Domiano Núñes,1 Robson Luis Oliveira Amorim,2 Manoel Jacobsen Teixeira,2 Mara Cristina Souza de Lucia,1 Almir Ferreira de Andrade,2 Wellingson Silva Paiva2 1Divisionof Psychology, Hospital das Clínicas, 2Divisionof Neurosurgery, University of São Paulo Medical School, São Paulo, Brazil Background: Diffuse axonal injury (DAI), a common cause of neurological sequelae in patients with traumatic brain injury (TBI), is considered one of the most prevalent forms of primary neuronal injury in patients with severe TBI. Cognitive deficits induced by DAI can persist over time, especially following moderate or severe injuries. The aim of the present study was to compare verbal fluency (VF) performance at6and12months after the trauma in a same group of patients with DAI. Methods: Eighteen patients with moderate to severe DAI and17healthy volunteers were enrolled. All DAI participants had sustained a TBI at least6months prior to the start of the study, were between18and50years of age, and had at least4years of education. The VF test was administered within an extensive neuropsychological test battery. We evaluated the same patients at6months (DAI1group) and12months (DAI2group) and compared the results of neuropsychological tests with a control group of healthy volunteers who were matched to patients for sex, age, and educational level. Results: In comparison to controls, the DAI1group produced significantly fewer words. The DAI2group produced significantly more semantic words than DAI1(P

A five-and-a-half-year-old girl started experiencing progressive left hemiparesis at age two and a half years. At age five years and four months she started presenting clusters of asymmetric periodic epileptic spasms with no hypsarrhythmia. The ictal EEG showed periodic, constant and stereotyped complexes. Serial brain imaging revealed progressive atrophy of the right hemisphere with increased T2 signal on MRI. She underwent a right hemispherotomy, and histological examination showed signs of inflammation and features of focal cortical dysplasia (FCD). She has been seizure-free for 16 months. This case is unique in the following aspects: the presence of typical Rasmussen encephalitis features of progressive unilateral brain involvement without seizures, a delay of almost three years prior to seizure onset; an atypical seizure type presentation with periodic epileptic spasms and the presence of FCD associated with inflammatory changes. [Published with video sequences].

Objective: The acute nootropic potential of donepezil in young healthy volunteers has not been adequately investigated mainly because in previous studies: (1) effects were assessed before peak-plasma concentration (Tmax) was reached; (2) only a few cognitive processes were assessed. Here we investigated a myriad of cognitive effects of augmentation of acetylcholine using an acute dose of donepezil in healthy adults at theoretical Tmax. Methods: This was a double-blind, placebo controlled, parallel group design study of cognitive effects of acute oral donepezil (5 mg). Subjects were tested twice after donepezil ingestion: 90 min (time that coincides with previous testing in the literature) and 210 min. (theoretical Tmax). The test battery included tasks that tap cognitive domains that are sensitive to acetylcholine manipulations. Results: At both testing times donepezil improved long-term recall of prose, objects recall, recall of spatial locations, and integration of objects with their locations, some effects having been related to self-reported mood enhancement. However, improvement of performance in the central executive measure (backward digit span) occurred only at Tmax. Conclusion: Positive cognitive effects of acute donepezil can be observed in various cognitive domains including mood, but its full nootropic potential is more clearly found close to theoretical peak-plasma concentration. Copyright © 2009 John Wiley & Sons, Ltd.