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Affective disorders (i.e. anxiety and depression) are commonly observed in patients with epilepsy and induce seizure aggravation. Animal models of epilepsy that exhibit affective disorder features are essential in developing new neuromodulatory treatments. GEAS-W rats (Generalized Epilepsy with Absence Seizures, Wistar background) are an inbred model of generalized epilepsy showing spontaneous spike-wave discharges concomitant with immobility. Transcranial Direct Current Stimulation (tDCS) is a safe non-invasive neuromodulatory therapy used to modulate dysfunctional circuitries frequently and successfully applied in affective disorders for symptom alleviation. Here we investigated anxiolytic and antidepressant effects of tDCS in GEAS-W rats and the role of corticosterone as a possible mechanism of action. GEAS-W and Wistar rats were randomly divided into control, sham-tDCS and active-tDCS groups. Both tDCS groups received 15 sessions of sham or active-tDCS (1 mA, cathode). Behavioural tests included the Open Field and Forced Swimming tests followed by corticosterone analysis. We observed a main effect of treatment and a significant treatment by strain interaction on anxiety-like and depressive-like behaviours, with active-tDCS GEAS-W rats entering the center of the open field more often and showing less immobility in the forced swimming test. Furthermore, there was a main effect of treatment on corticosterone with active-tDCS animals showing marked reduction in plasmatic levels. This study described preclinical evidence to support tDCS treatment of affective disorders in epilepsy and highlights corticosterone as a possible mechanism of action., (Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.)

Serotonin (5-HT) receptors have been implicated in responses to aversive stimuli in mammals and fish, but its precise role is still unknown. Moreover, since at least seven families of 5-HT receptors exist in vertebrates, the role of specific receptors is still debated. Aversive stimuli can be classified as indicators of proximal, distal, or potential threat, initiating responses that are appropriate for each of these threat levels. Responses to potential threat usually involve cautious exploration and increased alertness, while responses to distal and proximal threat involve a fight-flight-freeze reaction. We exposed adult zebrafish to a conspecific alarm substance (CAS) and observed behavior during (distal threat) and after (potential threat) exposure, and treated with the 5-HT 2C receptor agonists MK-212 or WAY-161503 or with the antagonist RS-102221. The agonists blocked CAS-elicited defensive behavior (distal threat), but not post-exposure increases in defensive behavior (potential threat), suggesting inhibition of responses to distal threat. MK-212 blocked changes in freezing elicited by acute restraint stress, a model of proximal threat, while RS-102221 blocked changes in geotaxis elicited this stressor. We also found that RS-102221, a 5-HT 2C receptor antagonist, produced small effect on behavior during and after exposure to CAS. Preprint: https://www.biorxiv.org/content/10.1101/2020.10.04.324202; Data and scripts: https://github.com/lanec-unifesspa/5-HT-CAS/tree/master/data/5HT2C., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Current theories on the role of serotonin (5-HT) in vertebrate defensive behavior suggest that this monoamine increases anxiety but decreases fear, by acting at different levels of the neuroaxis. This paradoxical, dual role of 5-HT suggests that a serotonergic tone inhibits fear responses, while an acute increase in 5-HT would produce anxiety-like behavior. However, so far no evidence for a serotonergic tone has been found. Using zebrafish alarm responses, we investigate the participation of phasic and tonic 5-HT levels in fear-like behavior, as well as in behavior after stimulation. Conspecific alarm substance (CAS) increased bottom-dwelling and erratic swimming, and animals transferred to a novel environment after CAS exposure (post-exposure behavior) showed increased bottom-dwelling and freezing. Clonazepam blocked CAS effects during and after exposure. Acute fluoxetine dose-dependently decreased fear-like behavior, but increased post-exposure freezing. Metergoline had no effect on fear-like behavior, but blocked the effects of CAS on post-exposure behavior; similar effects were observed with para-chlorophenylalanine. Finally, CAS was shown to decrease the activity of monoamine oxidase in the zebrafish brain after exposure. These results suggest that phasic and tonic serotonin encode an aversive expectation value, switching behavior toward cautious exploration/risk assessment/anxiety when the aversive stimulus is no longer present., (© 2020 International Society for Neurochemistry.)

Background and Purpose: In any given year, 28% to 35% of older adults experience falls. In nursing home environments, the annual rate of falls increases to 30% to 50%. Our objective was to verify and compare the reliability, validity, and ability to identify falls of the Berg Balance Scale (BBS), Balance Evaluation Systems Test (BESTest), Mini-BESTest, and Brief-BESTest for older adults who live in nursing homes., Methods: This was a cross-sectional study. Older adults (n = 49; aged 62-90 years; mean = 77.8; standard deviation = 7.2) were recruited from a nonprofit nursing home. All participants were assessed by 2 physiotherapists using the BBS, BESTest, Mini-BESTest, and Brief-BESTest. The interrater and test-retest (7-14 days) reliability were assessed using intraclass correlation coefficients (ICCs [2, 1]). Minimal detectable changes at the 95% confidence level were established. To analyze each test's ability to identify fall status, we used receiver operating characteristic (ROC) curves, whose statistical significance we verified using the area under the ROC curve (AUC) and respective 95% confidence intervals (CIs). The diagnostic likelihood ratios (positive and negative) and 95% CI were used to verify posttest probability. We used Fagan's nomogram to show the posttest probability of each balance test. Validity was assessed using kappa coefficients and the prevalence-adjusted bias-adjusted kappa (PABAK)., Results: Interrater and test-retest reliability for the total scores were good to excellent across all 4 tests (ICC interrater value = 0.992-0.994 and ICC test-retest value = 0.886-0.945). All tests were also able to identify fall status (AUC = 0.712-0.762) and were in good agreement with each other (kappa coefficient for individuals with fall risk = 0.679-0.957 and individuals with no fall risk = 0.135-0.143; PABAK = 83.7%-98%)., Conclusion: All balance tests presented similar reliability, reproducibility, and validity. This suggests that any of these tests can be used in clinical practice. However, the Brief-BESTest is the quickest and easiest test to perform.

Background: Recently, interactive video games (IVGs) have been used as a health-care intervention that provides both exercise and cognitive stimulation. Several studies have shown that IVGs can improve postural control, gait, cognition, and functional independence in elderly people and patients with neurological disease. However, there is a lack of evidence about the effects of IVGs on frail and pre-frail elderly people. The aim of this study was to evaluate the feasibility, safety, and acceptability of playing Nintendo Wii Fit Plus ™ (NWFP) interactive video games, and the functional outcomes (postural control, gait, cognition, mood, and fear of falling) in frail and pre-frail older adults., Methods: This study is a randomized controlled, parallel-group, feasibility trial. Participants were frail and pre-frail older adults randomly assigned to the experimental group (EG, n = 15) or control group (CG, n = 15). Participants in the EG performed 14 training sessions, lasting 50 min each, twice a week. In each training session, participants played five of 10 selected games, with two attempts at each game. Participants in the CG received general advice regarding the importance of physical activity. All participants were assessed on three occasions by a blinded physical therapist: before and after intervention, and 30 days after the end of the intervention (follow-up). We assessed the feasibility (score of participants in the games), acceptability (game satisfaction questionnaire), safety (adverse events during training sessions), and functional outcomes: (1) postural control (Mini-BESTest); (2) gait (Functional Gait Assessment); (3) cognition (Montreal Cognitive Assessment); (4) mood (GDS-15); and (5) fear of falling (FES-I)., Results: Participants in the EG improved their scores in all 10 games, reported that they understood and enjoyed the tasks of the games, and presented few adverse events during the practice. There was a significant improvement in the Mini-BESTest and Functional Gait Assessment in the EG when compared with the CG (p < 0.05)., Conclusion: The use of NWFP was feasible, acceptable, and safe for frail older adults and improved their postural control and gait. There were no effects on cognition, mood, or fear of falling. This trial was registered in the Brazilian Registry of Clinical Trials (RBR-823rst) on 11 June 2016., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To compare the effectiveness of Kinect Adventures games versus conventional physiotherapy to improve postural control (PC), gait, cardiorespiratory fitness, and cognition of the elderly. In addition, we evaluated the safety, acceptability, and adherence to the interventions., Materials and Methods: The study was a randomized clinical trial in which 46 elderly individuals were selected, mean age 69.3 (5.34) years. Participants were allocated to the Kinect Adventures Training Group (KATG) or the Conventional Physical Therapy Group (CPTG), 23 individuals in each group. Participants of both groups participated in 14 training sessions lasting 1 hour each, twice a week. The KATG practiced four Kinect Adventures games. The CPTG participated in conventional physiotherapy. The primary outcome was PC: Mini-Balance Evaluation Systems Test (Mini-BESTest), and secondary outcomes were gait: Functional Gait Assessment (FGA), cardiorespiratory fitness: Six-minute step test (6MST), and cognition: Montreal Cognitive Assessment (MoCA). Acceptability was assessed through a questionnaire created by the researchers themselves. Adherence was assessed by the "frequency of the number of elderly individuals who completed the interventions and safety through the presence of adverse effects." Participants were assessed immediately pre- and posttreatment and fourth week after the end of the treatment. Statistical analysis was done through repeated-measures analysis of variance and Tukey post hoc test., Results: Both groups presented a significant improvement in the PC (Mini-BEST), gait (FGA), and cognition (MoCA) posttreatment that was maintained at fourth week after treatment (post hoc Tukey test; P < 0.05). Regarding cardiorespiratory fitness (6MST), the KATG presented improvement posttreatment and maintenance of the results in the fourth week after treatment. CPTG showed improvement only in fourth week after treatment (post hoc Tukey tests; P < 0.05). Regarding the acceptability, the questionnaire showed that both groups were satisfied with regard to the proposed interventions. There was 91% adherence in both training sessions. Regarding the safety, 34% and 26% of the individuals of the KATG and CPTG, respectively, presented adverse effects of delayed muscle pain in the lower limbs after the first session only., Conclusion: There were no significant differences between the KATG and CPTG; both interventions provided positive effects on PC, gait, cardiorespiratory fitness, and cognition of the elderly.

Background: Frailty can be defined as a medical syndrome with multiple causes and contributors, characterized by diminished strength and endurance and reduced physiological function that increases the vulnerability to develop functional dependency and/or death. Studies have shown that the most commonly studied exercise protocol for frail older adults is the multimodal training. Interactive video games (IVGs) involve tasks in virtual environments that combine physical and cognitive demands in an attractive and challenging way. The aim of this study will be to evaluate the feasibility, safety, acceptability, and functional outcomes of playing Nintendo Wii Fit Plus TM (NWFP) for frail older adults., Methods/design: The study is a randomized controlled, parallel group, feasibility trial. Participants will be randomly assigned to the experimental group (EG) and control group (CG). The EG will participate in 14 training sessions, each lasting 50 min, twice a week. In each training session, the participants will play five games, with three attempts at each game. The first attempt will be performed with the assistance of a physical therapist to correct the movements and posture of the patients and subsequent attempts will be performed independently. Scores achieved in the games will be recorded. The participants will be evaluated by a blinded physical therapist at three moments: before and after intervention and 30 days after the end of the intervention (follow-up). We will assess the feasibility, acceptability, safety, and clinical outcomes (postural control, gait, cognition, quality of life, mood, and fear of falling)., Discussion: Due to the deficiencies in multiple systems, studies have shown that multimodal interventions including motor-cognitive stimulation can improve the mobility of frail elderly adults. IVGs, among them the NWFP, are considered as a multimodal motor-cognitive intervention that can potentially improve motor and cognitive functions in the frail elderly. However, there is still no evidence in the literature that proves the feasibility, safety, acceptability, and functional outcomes of this intervention in frail elderly individuals., Trial Registration: Brazilian Registry of Clinical Trials (RBR-823rst). World Health Organization Trial Registration Data Set (Additional file 1).