Stuttering treatment control using P300 event-related potentials

Positron emission tomography studies during speech have indicated a failure to show the normal activation of auditory cortical areas in stuttering individuals. In the present study, P300 event-related potentials were used to investigate possible effects of behavioral treatment on the pattern of signal amplitude and latency between waves. In order to compare variations in P300 measurements, a control group paired by age and gender to the group of stutterers, was included in the study. Findings suggest that the group of stutterers presented a significant decrease in stuttering severity after the fluency treatment program. Regarding P300 measurements, stutterers and their controls presented results within normal limits in all testing situations and no significant statistical variations between pre and post treatment testing. When comparing individual results between the testing situations, stutterers presented a higher average decrease in wave latency for the right ear following treatment. The results are discussed in light of previous P300 event-related potentials and functional imaging studies with stuttering adults. Educational objectives: The reader will learn about and be able to describe the: (1) use of P300 event-related potentials in the study of stuttering; (2) differences between stuttering and non-stuttering adults; and (3) effects of behavioral fluency treatment on cerebral activity in stuttering speakers. (C) 2011 Elsevier Inc. All rights reserved.

Cannabis use before age 15 and subsequent executive functioning

Background Many studies have suggested that adolescence is a period of particular vulnerability to neurocognitive effects associated with substance misuse. However, few large studies have measured differences in cognitive performance between chronic cannabis users who started in early adolescence (before age 15) with those who started later. Aims To examine the executive functioning of individuals who started chronic cannabis use before age 15 compared with those who started chronic cannabis use after 15 and controls. Method We evaluated the performance of 104 chronic cannabis users (49 early-onset users and 55 late-onset users) and 44 controls who undertook neuropsychological tasks, with a focus on executive functioning. Comparisons involving neuropsychological measures were performed using generalised linear model analysis of variance (ANOVA). Results The early-onset group showed significantly poorer performance compared with the controls and the late-onset group on tasks assessing sustained attention, impulse control and executive functioning. Conclusions Early-onset chronic cannabis users exhibited poorer cognitive performance than controls and late-onset users in executive functioning. Chronic cannabis use, when started before age 15, may have more deleterious effects on neurocognitive functioning.

Influence of silence and attention on tinnitus perception

OBJECTIVE: The purpose of this study was to study the effect of attention and sustained silence on the emergence of auditory phantom perception in normal-hearing adults. STUDY DESIGN: Cross-sectional survey. SUBJECTS AND METHODS: While sitting in a sound booth, 66 volunteers (age range. 18-65; mean age, 37.3) performed 3 experiments of 5 minutes each, consecutively and randomly presented. Two deviated attention from auditory system (Hanoi and visual attention experiments). and 1 drove attention to the auditory system (auditory attention). After each experiment, participants were asked about their auditory and visual perception. No sound or light change was given at any moment. RESULTS: Of the participants, 19.7% experienced tinnitus during Hanoi, 45.5% during visual attention, and 68.2% during auditory attention experiment. with no significant differences for studied variables. CONCLUSION: Tinnitus-like perceptions may occur in a non-clinical population in a silent environment. Concomitant auditory attention plays an important role on the emergence of tinnitus. (C) 2008 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved.

Lateral asymmetry of voluntary attention orienting

We recently demonstrated that automatic attention favors the right side of space and, in the present study, we investigated whether voluntary attention also favors this side. Six reaction time experiments were conducted. In each experiment, 12 new 18-25-year-old male right-handed individuals were tested. In Experiments 1, 2, 3 (a, b) and 4 (a, b), tasks with increasing attentional demands were used. In Experiments 1, 2, 3a, and 4a, attention was oriented to one or both sides by means of a central spatially informative visual cue. A left or right side visual target appeared 100, 300, or 500 ms later. Attentional effects were observed in the four experiments. In Experiments 2, 3a and 4a, these effects were greater when the cue indicated the right side than when it indicated the left side (respectively: 16 ± 10 and 44 ± 6 ms, P = 0.015, for stimulus onset asynchrony of 500 ms in Experiment 2; 38 ± 10 and 70 ± 7 ms, P = 0.011, for Experiment 3a, and 23 ± 11 and 61 ± 10 ms, P = 0.009, for Experiment 4a). In Experiments 3b and 4b, the central cue pointed to both sides and was said to be non-relevant for task performance. In these experiments right and left reaction times did not differ. The most conservative interpretation of the present findings is that voluntary attention orienting favors the right side of space, particularly when a difficult task has to be performed.

Evidence for divided automatic attention

A long-standing debate in the literature is whether attention can form two or more independent spatial foci in addition to the well-known unique spatial focus. There is evidence that voluntary visual attention divides in space. The possibility that this also occurs for automatic visual attention was investigated here. Thirty-six female volunteers were tested. In each trial, a prime stimulus was presented in the left or right visual hemifield. This stimulus was characterized by the blinking of a superior, middle or inferior ring, the blinking of all these rings, or the blinking of the superior and inferior rings. A target stimulus to which the volunteer should respond with the same side hand or a target stimulus to which she should not respond was presented 100 ms later in a primed location, a location between two primed locations or a location in the contralateral hemifield. Reaction time to the positive target stimulus in a primed location was consistently shorter than reaction time in the horizontally corresponding contralateral location. This attentional effect was significantly smaller or absent when the positive target stimulus appeared in the middle location after the double prime stimulus. These results suggest that automatic visual attention can focus on two separate locations simultaneously, to some extent sparing the region in between.

Minor and Unsystematic Cortical Topographic Changes of Attention Correlates between Modalities

In this study we analyzed the topography of induced cortical oscillations in 20 healthy individuals performing simple attention tasks. We were interested in qualitatively replicating our recent findings on the localization of attention-induced beta bands during a visual task [1], and verifying whether significant topographic changes would follow the change of attention to the auditory modality. We computed corrected latency averaging of each induced frequency bands, and modeled their generators by current density reconstruction with Lp-norm minimization. We quantified topographic similarity between conditions by an analysis of correlations, whereas the inter-modality significant differences in attention correlates were illustrated in each individual case. We replicated the qualitative result of highly idiosyncratic topography of attention-related activity to individuals, manifested both in the beta bands, and previously studied slow potential distributions [2]. Visual inspection of both scalp potentials and distribution of cortical currents showed minor changes in attention-related bands with respect to modality, as compared to the theta and delta bands, known to be major contributors to the sensory-related potentials. Quantitative results agreed with visual inspection, supporting to the conclusion that attention-related activity does not change much between modalities, and whatever individual changes do occur, they are not systematic in cortical localization across subjects. We discuss our results, combined with results from other studies that present individual data, with respect to the function of cortical association areas.

An external focus of attention results in greater swimming speed

We examined effects of attentional focus on swimming speed. Participants` task was to swim one length of a pool (16 m) using the front crawl stroke. In Experiment 1, intermediate swimmers were given attentional focus instructions related to the crawl arm stroke or the leg kick, respectively. Participants were instructed to focus on ""pulling your hands back"" or ""pushing the instep down"" (internal focus), or on ""pushing the water back/down"" (external focus), respectively. Swim times were significantly shorter with an external focus. In Experiment 2, a control condition was included. Times were significantly faster in the external focus compared with both the internal focus and control conditions. These findings have implications for enhancing performance in swimming.

In situ gelling hexagonal phases for sustained release of an anti-addiction drug

In this study, fluid precursor formulations for subcutaneous injection and in situ formation of hexagonal phase gels upon water absorption were developed as a strategy to sustain the release of naltrexone, a drug used for treatment of drug addiction. Precursor formulations were obtained by combining BRIJ 97 with propylene glycol (PG, 5-70%, w/w). To study the phase behavior of these formulations, water was added at 10-90% (w/w), and the resulting systems were characterized by polarized light microscopy. Two precursor formulations containing BRIJ:PG at 95:5 (w/w, referred to as BRIJ-95) and at 80:20 (w/w, referred to as BRIJ-80) were chosen. Naltrexone was dissolved at 1% or suspended at 5% (w/w). Precursor formulations were transformed into hexagonal phases when water content exceeded 20%. Water uptake followed second-order kinetics, and after 2-4 h all precursor formulations were transformed into hexagonal phases. Drug release was prolonged by the precursor formulations (compared to a drug solution in PBS), and followed pseudo-first order kinetics regardless of naltrexone concentration. The release from BRIJ-80 was significantly higher than that from BRIJ-95 after 48 h. The relative safety of the precursor formulations was assessed in cultured fibroblasts. Even though BRIJ-95 was more cytotoxic than BRIJ-80, both precursor formulations were significantly less cytotoxic than sodium lauryl sulfate (considered moderate-to-severe irritant) at the same concentration (up to 50 mu g/mL). These results suggest the potential of BRIJ-based precursor formulations for sustained naltrexone release. (C) 2011 Elsevier By. All rights reserved.

Sustained release carriers used to delivery bone morphogenetic proteins in the bone healing process

Bone morphogenetic proteins (BMPs) are multi-functional growth factors belonging to the transforming growth factor beta superfamily, especially BMP-2, induce bone formation in vivo, and clinical application in repair of bone fractures and defects is expected. However, appropriate systems to delivery BMPs for practical use need to be developed with the objective to heal cartilage and bone-related diseases in medical, dental and veterinary practice. Thus, the aim of this article was to present an overview of the principals carriers used to delivery BMPs and alternative delivery systems for these proteins.

Visuospatial attention disturbance in Duchenne muscular dystrophy

AIM The cognitive deficits present in the Duchenne muscular dystrophy (DMD) are not yet well characterized. Attention, considered to be the brain mechanism responsible for the selection of sensory stimuli, could be disturbed in DMD, contributing, at least partially, to the observed global cognitive deficit. The aim of this study was to investigate attentional function in individuals with DMD. METHOD Twenty-five males (mean age 12y; SD 2y 2mo) with DMD and 25 healthy males (mean age 12y; SD 2y) were tested in a visuospatial task (Posner computerized test). They were instructed to respond as quickly as possible to a lateralized visual target stimulus with the ipsilateral hand. Their attention was automatically orientated by a peripheral prime stimulus or, alternatively, voluntarily orientated by a central spatially informative cue. RESULTS The main result obtained was that the attentional effect (sum of the benefit and the cost of attention) did not differ between the two groups in the case of automatic attention (p=0.846) but was much larger for individuals with DMD than for comparison individuals in the case of voluntary attention (p < 0.001). INTERPRETATION The large voluntary attentional effect exhibited by the participants with DMD seems similar to that of younger children, suggesting that the disease is associated with delayed maturation of voluntary attention mechanisms.

Rehabilitation of executive dysfunction: A controlled trial of an attention and problem solving treatment group

In this study, the effectiveness of a group-based attention and problem solving (APS) treatment approach to executive impairments in patients with frontal lobe lesions was investigated. Thirty participants with lesions in the frontal lobes, 16 with left frontal (LF) and 14 with right frontal (RF) lesions, were allocated into three groups, each with 10 participants. The APS treatment was initially compared to two other control conditions, an information/education (IE) approach and treatment-as-usual or traditional rehabilitation (TR), with each of the control groups subsequently receiving the APS intervention in a crossover design. This design allowed for an evaluation of the treatment through assessment before and after treatment and on follow up, six months later. There was an improvement on some executive and functional measures after the implementation of the APS programme in the three groups. Size, and to a lesser extent laterality, of lesion affected baseline performance on measures of executive function, but there was no apparent relationship between size, laterality or site of lesion and level of benefit from the treatment intervention. The results were discussed in terms of models of executive functioning and the effectiveness of domain specific interventions in the rehabilitation of executive dysfunction.

Do Phenotypic Characteristics, Parental Psychopathology, Family Functioning, and Environmental Stressors Have a Role in the Response to Methylphenidate in Children With Attention-Deficit/Hyperactivity Disorder? A Naturalistic Study From a Developing Country

Little is known about the effect of clinical characteristics, parental psychopathology, family functioning, and environmental stressors in the response to methylphenidate in children with attention-deficit/hyperactivity disorder (ADHD) followed up in a naturalistic setting. Data from cultures outside the United States are extremely scarce. This is a longitudinal study using a nonrandom assignment, quasi-experimental design. One hundred twenty-five children with ADHD were treated with methylphenidate according to standard clinical procedures, and followed up for 6 months. The severity of ADHD symptoms was assessed by the Swanson, Nolan, and Pelham rating scale. In the final multivariate model, ADHD combined subtype (P < 0.001) and comorbidity with oppositional defiant disorder (P = 0.03) were both predictors of a worse clinical response. In addition, the levels of maternal ADHD symptoms were also associated with worse prognosis (P < 0.001). In the context of several adverse psychosocial factors assessed, only undesired pregnancy was associated with poorer response to methylphenidate in the final comprehensive-model (P = 0.02). Our study provides evidence for the involvement of clinical characteristics, maternal psychopathology, and environmental stressors in the response to methylphenidate. Clinicians may consider adjuvant strategies when negative predictors are present to increase the chances of success with methylphenidate treatment.

A NEUROECONOMIC MODELING OF ATTENTION-DEFICIT/HYPERACTIVITY DISORDER (ADHD)

In this paper we present a new neuroeconomics model for decision-making applied to the Attention-Deficit/Hyperactivity Disorder (ADHD). The model is based on the hypothesis that decision-making is dependent on the evaluation of expected rewards and risks assessed simultaneously in two decision spaces: the personal (PDS) and the interpersonal emotional spaces (IDS). Motivation to act is triggered by necessities identified in PDS or IDS. The adequacy of an action in fulfilling a given necessity is assumed to be dependent on the expected reward and risk evaluated in the decision spaces. Conflict generated by expected reward and risk influences the easiness (cognitive effort) and the future perspective of the decision-making. Finally, the willingness (not) to act is proposed to be a function of the expected reward (or risk), adequacy, easiness and future perspective. The two most frequent clinical forms are ADHD hyperactive (AD/HDhyp) and ADHD inattentive (AD/HDdin). AD/HDhyp behavior is hypothesized to be a consequence of experiencing high rewarding expectancies for short periods of time, low risk evaluation, and short future perspective for decision-making. AD/HDin is hypothesized to be a consequence of experiencing high rewarding expectancies for long periods of time, low risk evaluation, and long future perspective for decision-making.

A Sustained Virologic Response Is Durable in Patients With Chronic Hepatitis C Treated With Peginterferon Alfa-2a and Ribavirin

BACKGROUND & AIMS: A sustained virologic response (SVR) to therapy for hepatitis C virus (HCV) infection is defined as the inability to detect HCV RNA 24 weeks after completion of treatment. Although small studies have reported that the SVR is durable and lasts for long periods, it has not been conclusively shown. METHODS: The durability of treatment responses was examined in patients originally enrolled in one of 9 randomized multicenter trials (n = 1343). The study included patients who received pegylated interferon (peginterferon) alfa-2a alone (n = 166) or in combination with ribavirin (n = 1077, including 79 patients with normal alanine aminotransferase levels and 100 patients who were coinfected with human immunodeficiency virus and HCV) and whose serum samples were negative for HCV RNA (<50 IU/mL) at their final assessment. Patients were assessed annually, from the date of last treatment, for a mean of 3.9 years (range, 0.8-7.1 years). RESULTS: Most patients (99.1%) who achieved an SVR had undetectable levels of HCV RNA in serum samples throughout the follow-up period. Serum samples from 0.9% of the patients contained HCV RNA a mean of 1.8 years (range, 1.1-2.9 years) after treatment ended. It is not clear if these patients were reinfected or experienced a relapse. CONCLUSIONS: In a large cohort of patients monitored for the durability of an SVR, the SVR was maintained for almost 4 years after treatment with peginterferon alfa-2a alone or in combination with ribavirin. In patients with chronic hepatitis C infection, the SVR is durable and these patients should be considered as cured.

Exercise training inhibits inflammatory cytokines and more than prevents myocardial dysfunction in rats with sustained beta-adrenergic hyperactivity

Myocardial hypertrophy and dysfunction occur in response to excessive catecholaminergic drive. Adverse cardiac remodelling is associated with activation of proinflammatory cytokines in the myocardium. To test the hypothesis that exercise training can prevent myocardial dysfunction and production of proinflammatory cytokines induced by beta-adrenergic hyperactivity, male Wistar rats were assigned to one of the following four groups: sedentary non-treated (Con); sedentary isoprenaline treated (Iso); exercised non-treated (Ex); and exercised plus isoprenaline (Iso+Ex). Echocardiography, haemodynamic measurements and isolated papillary muscle were used for functional evaluations. Real-time RT-PCR and Western blot were used to quantify tumour necrosis factor alpha, interleukin-6, interleukin-10 and transforming growth factor beta(1) (TGF-beta(1)) in the tissue. NF-kappa B expression in the nucleus was evaluated by immunohistochemical staining. The Iso rats showed a concentric hypertrophy of the left ventricle (LV). These animals exhibited marked increases in LV end-diastolic pressure and impaired myocardial performance in vitro, with a reduction in the developed tension and maximal rate of tension increase and decrease, as well as worsened recruitment of the Frank-Starling mechanism. Both gene and protein levels of tumour necrosis factor alpha and interleukin-6, as well as TGF-beta(1) mRNA, were increased. In addition, the NF-kappa B expression in the Iso group was significantly raised. In the Iso+Ex group, the exercise training had the following effects: (1) it prevented LV hypertrophy; (ii) it improved myocardial contractility; (3) it avoided the increase of proinflammatory cytokines and improved interleukin-10 levels; and (4) it attenuated the increase of TGF-beta(1) mRNA. Thus, exercise training in a model of beta-adrenergic hyperactivity can avoid the adverse remodelling of the LV and inhibit inflammatory cytokines. Moreover, the cardioprotection is related to beneficial effects on myocardial performance.