Bursts of vagus nerve stimulation paired with auditory rehabilitation fail to improve speech sound perception in rats with hearing loss.

Hearing loss can lead to long-lasting effects on the central nervous system, and current therapies, such as auditory training and rehabilitation, show mixed success in improving perception and speech comprehension. Vagus nerve stimulation (VNS) is an adjunctive therapy that can be paired with rehabilitation to facilitate behavioral recovery after neural injury. However, VNS for auditory recovery has not been tested after severe hearing loss or significant damage to peripheral receptors. This study investigated the utility of pairing VNS with passive or active auditory rehabilitation in a rat model of noise-induced hearing loss. Although auditory rehabilitation helped rats improve their frequency discrimination, learn novel speech discrimination tasks, and achieve speech-in-noise performance similar to normal hearing controls, VNS did not enhance recovery of speech sound perception. These results highlight the limitations of VNS as an adjunctive therapy for hearing loss rehabilitation and suggest that optimal benefits from neuromodulation may require restored peripheral signaling.

Climate system asymmetries drive eccentricity pacing of hydroclimate during the early Eocene greenhouse.

The early Eocene Climatic Optimum (EECO) represents the peak of Earth's last sustained greenhouse climate interval. To investigate hydroclimate variability in western North America during the EECO, we developed an orbitally resolved leaf wax δ2H record from one of the most well-dated terrestrial paleoclimate archives, the Green River Formation. Our δ2Hwax results show ∼60‰ variation and evidence for eccentricity and precession forcing. iCESM simulations indicate that changes in the Earth's orbit drive large seasonal variations in precipitation and δ2H of precipitation at our study site, primarily during the summer season. Our findings suggest that the astronomical response in δ2Hwax is attributable to an asymmetrical climate response to the seasonal cycle, a "clipping" of precession forcing, and asymmetric carbon cycle dynamics, which further enhance the influence of eccentricity modulation on the hydrological cycle during the EECO. More broadly, our study provides an explanation for how and why eccentricity emerges as a dominant frequency in climate records from ice-free greenhouse worlds.

Precise sound characteristics drive plasticity in the primary auditory cortex with VNS-sound pairing.

Introduction: Repeatedly pairing a tone with vagus nerve stimulation (VNS) alters frequency tuning across the auditory pathway. Pairing VNS with speech sounds selectively enhances the primary auditory cortex response to the paired sounds. It is not yet known how altering the speech sounds paired with VNS alters responses. In this study, we test the hypothesis that the sounds that are presented and paired with VNS will influence the neural plasticity observed following VNS-sound pairing. Methods: To explore the relationship between acoustic experience and neural plasticity, responses were recorded from primary auditory cortex (A1) after VNS was repeatedly paired with the speech sounds 'rad' and 'lad' or paired with only the speech sound 'rad' while 'lad' was an unpaired background sound. Results: Pairing both sounds with VNS increased the response strength and neural discriminability of the paired sounds in the primary auditory cortex. Surprisingly, pairing only 'rad' with VNS did not alter A1 responses. Discussion: These results suggest that the specific acoustic contrasts associated with VNS can powerfully shape neural activity in the auditory pathway. Methods to promote plasticity in the central auditory system represent a new therapeutic avenue to treat auditory processing disorders. Understanding how different sound contrasts and neural activity patterns shape plasticity could have important clinical implications.

Effects of emotional context on impulse control.

High risk behaviors such as narcotic use or physical fighting can be caused by impulsive decision making in emotionally-charged situations. Improved neuroscientific understanding of how emotional context interacts with the control of impulsive behaviors may lead to advances in public policy and/or treatment approaches for high risk groups, including some high-risk adolescents or adults with poor impulse control. Inferior frontal gyrus (IFG) is an important contributor to response inhibition (behavioral impulse control). IFG also has a role in processing emotional stimuli and regulating emotional responses. The mechanism(s) whereby response inhibition processes interact with emotion processing in IFG are poorly understood. We used 4.7 T fMRI in 20 healthy young adults performing a rapid event-related emotional Go/NoGo task. This task combined the Go/NoGo task, which is a classic means of recruiting response inhibition processes, with emotionally neutral and aversive distractor images. In IFG, both response inhibition in an emotionally neutral context (neutral NoGo trials) and aversive emotional picture processing (aversive Go trials) evoked activation greater than the simple response baseline (neutral Go trials). These results are consistent with the literature. Activation for response inhibition in aversive contexts (aversive NoGo-neutral Go trials) was approximately the sum of response inhibition activation (neutral NoGo-neutral Go) and aversive emotional distractor activation (aversive Go-neutral Go). We conclude that response inhibition and aversive emotional stimulus processing activities combine additively (linearly) in IFG, rather than interfering with each other (sub-linearly) or mutually-enhancing each other (super-linearly). We also found previously undocumented interaction effects between response inhibition (NoGo vs. Go) and emotional context (aversive vs. neutral distractor pictures) in bilateral posterior middle temporal gyrus and angular gyrus, right frontal eye field, and other brain regions. These results may reflect the interaction of attention processes driven by emotional stimuli with conflict resolution processes related to Go/NoGo performance.

Canadian guidelines for the evidence-based treatment of tic disorders: behavioural therapy, deep brain stimulation, and transcranial magnetic stimulation.

This clinical guideline provides recommendations for nonpharmacological treatments for tic disorders. We conducted a systematic literature search for clinical trials on the treatment of tics. One evidence-based review (including 30 studies) and 3 studies on behavioural interventions, 3 studies on deep brain stimulation (DBS), and 3 studies on transcranial magnetic stimulation (TMS) met our inclusion criteria. Based on this evidence, we have made strong recommendations for the use of habit reversal therapy and exposure and response prevention, preferably embedded within a supportive, psychoeducational program, and with the option to combine either of these approaches with pharmacotherapy. Although evidence exists for the efficacy of DBS, the quality of this evidence is poor and the risks and burdens of the procedure are finely balanced with the perceived benefits. Our recommendation is that this intervention continues to be considered an experimental treatment for severe, medically refractory tics that have imposed severe limitations on quality of life. We recommend that the procedure should only be performed within the context of research studies and by physicians expert in DBS programming and in the management of tics. There is no evidence to support the use of TMS in the treatment of tics. However, the procedure is associated with a low rate of known complications and could continue to be evaluated within research protocols. The recommendations we provide are based on current knowledge, and further studies may result in their revision in future.

Canadian guidelines for the evidence-based treatment of tic disorders: pharmacotherapy.

This article seeks to provide the practising clinician with guidance on the pharmacological management of tic disorders in children and adults. We performed a systematic review of the literature on the treatment of tic disorders. A multi-institutional group of 14 experts in psychiatry, child psychiatry, neurology, pediatrics, and psychology engaged in a consensus meeting. The evidence was presented and discussed, and nominal group techniques were employed to arrive at consensus on recommendations. A strong recommendation is made when the benefits of treatment clearly outweigh the risks and burdens, and can apply to most patients in most circumstances without reservation. With a weak recommendation, the benefits, risks, and burdens are more closely balanced, and the best action may differ depending on the circumstances. Based on these principles, weak recommendations were made for the use of pimozide, haloperidol, fluphenazine, metoclopramide (children only), risperidone, aripiprazole, olanzapine, quetiapine, ziprasidone, topiramate, baclofen (children only), botulinum toxin injections, tetrabenazine, and cannabinoids (adults only). Strong recommendations were made for the use of clonidine and guanfacine (children only). While the evidence supports the efficacy of many of the antipsychotics for the treatment of tics, the high rates of side effects associated with these medications resulted in only weak recommendations for these drugs. In situations where tics are not severe or disabling, the use of a medication with only a weak recommendation is not warranted. However, when tics are more distressing and interfering, the need for tic suppression to improve quality of life is stronger, and patients and clinicians may be more willing to accept the risks of pharmacotherapy.

fMRI investigation of response inhibition, emotion, impulsivity, and clinical high-risk behavior in adolescents.

High-risk behavior in adolescents is associated with injury, mental health problems, and poor outcomes in later life. Improved understanding of the neurobiology of high-risk behavior and impulsivity shows promise for informing clinical treatment and prevention as well as policy to better address high-risk behavior. We recruited 21 adolescents (age 14-17) with a wide range of high-risk behavior tendencies, including medically high-risk participants recruited from psychiatric clinics. Risk tendencies were assessed using the Adolescent Risk Behavior Screen (ARBS). ARBS risk scores correlated highly (0.78) with impulsivity scores from the Barratt Impulsivity scale (BIS). Participants underwent 4.7 Tesla functional magnetic resonance imaging (fMRI) while performing an emotional Go/NoGo task. This task presented an aversive or neutral distractor image simultaneously with each Go or NoGo stimulus. Risk behavior and impulsivity tendencies exhibited similar but not identical associations with fMRI activation patterns in prefrontal brain regions. We interpret these results as reflecting differences in response inhibition, emotional stimulus processing, and emotion regulation in relation to participant risk behavior tendencies and impulsivity levels. The results are consistent with high impulsivity playing an important role in determining high risk tendencies in this sample containing clinically high-risk adolescents.

Evidence for Involvement of Protein Kinase C in Germinal Vesicle Breakdown in Chaetopterus: (protein kinase C/phorbol ester/oocyte maturation).

We have examined the possible involvement of protein kinase C (C-kinase) in the initiation of germinal vesicle breakdown (GVBD) in Chaetopterus oocytes. Two tumor-promoting phorbol esters (phorbol-12, 13-dibezoate and 12-0-tetradecanoylphorbol-13-acetate [TPA]) and a permeant diacylglycerol (1-oleoyl-2-acetylglycerol), potent activators of C-Kinase, triggered GVBD. Two other phorbol esters (phorbol-13-monoacetate and 4α-phorbol-12, 13-didecanoate), which do not activate C-kinase, were inactive. Three C-kinase antagonists (W-7, H-7 and retinol) inhibited both naturally-and TPA-induced GVBD, whereas W-5, a much less inhibitory W-7 analog, had no effect on GVBD. Triggering of GVBD by TPA was independent of extracellular Ca2+ . Although naturally-induced GVBD was blocked by micromolar concentrations of the calmodulin antagonist, calmidazolium (R24571), and by millimolar concentrations of the permeant cAMP analog, dibutryryl cAMP, TPA-induced GVBD was not affected by these agents. These results support the hypothesis that both C-kinase and calmodulin are involved in the sequence of events leading to GVBD in this species.

Screen-printable silver pastes with metallic nano-zinc and nano-zinc alloys for crystalline silicon photovoltaic cells.

Silver metallization pastes for crystalline silicon PV cells containing nanosized metallic zinc were found to be superior to commercial pastes containing micrometer-sized metallic zinc and micrometer sized zinc oxide in terms of efficiency and firing window. Efficiency performance decreases as the size of the particles increases: nano-Zn > 3.6 µm Zn > 4.4 µm Zn. Advanced electron microscopy techniques were used to investigate the interfacial microstructure between the front-side contact and the Si emitter of nanosized zinc additive based cells fired at temperatures from below to above optimal. These microstructural observations confirmed the possibility of a tunneling mechanism of current flow (a "nano-Ag colloid assisted tunneling" model) in the absence of Ag crystallites. Contact resistance maps were used to guide sampling, leading to a better understanding of the relationship between microstructure and contact resistance. Low contact resistance and higher cell efficiency, especially at under- and overfiring temperature conditions, are due to more uniform silicon nitride etching obtained through the use of nanosized metallic zinc additives.

Neuropsychological functioning in children with Tourette syndrome (TS).

OBJECTIVE: We examined whether children with Tourette syndrome (TS) displayed a unique pattern of neuropsychological deficits on the CANTAB relative to control children. We also looked at whether children with TS and other comorbidities had more neuropsychological impairments than those with uncomplicated TS and how age was related to the profile of neuropsychological deficits in TS. METHOD: Participants included 38 children with TS (aged 7 to 13 years) and 38 control children (aged 6 to 12 years). All children were administered 8 subtests from the CANTAB and parents and teachers completed the BRIEF rating scale on children in the TS group. RESULTS: Children with TS displayed deficits relative to control children on measures of visual memory, executive functioning, and attention from the CANTAB. Among the TS group, age was negatively correlated with performance on measures of executive functioning, speed of response and working memory. CONCLUSIONS: Identifying the pattern of neuropsychological deficits in children with TS on the CANTAB is important for highlighting areas of deficit that can be targeted for intervention and teaching strategies. With further research, the CANTAB may prove to be a useful resource in the assessment and treatment of children with TS.

Risperidone in the treatment of disruptive behavioral symptoms in children with autistic and other pervasive developmental disorders.

OBJECTIVE: To investigate the efficacy and safety of risperidone for the treatment of disruptive behavioral symptoms in children with autism and other pervasive developmental disorders (PDD). METHODS: In this 8-week, randomized, double-blind, placebo-controlled trial, risperidone/placebo solution (0.01-0.06 mg/kg/day) was administered to 79 children who were aged 5 to 12 years and had PDD. Behavioral symptoms were assessed using the Aberrant Behavior Checklist (ABC), Nisonger Child Behavior Rating Form, and Clinical Global Impression-Change. Safety assessments included vital signs, electrocardiogram, extrapyramidal symptoms, adverse events, and laboratory tests. RESULTS: Subjects who were taking risperidone (mean dosage: 0.04 mg/kg/day; 1.17 mg/day) experienced a significantly greater mean decrease on the irritability subscale of the ABC (primary endpoint) compared with those who were taking placebo. By study endpoint, risperidone-treated subjects exhibited a 64% improvement over baseline in the irritability score almost double that of placebo-treated subjects (31%). Risperidone-treated subjects also exhibited significantly greater decreases on the other 4 subscales of the ABC; on the conduct problem, insecure/anxious, hyperactive, and overly sensitive subscales of the Nisonger Child Behavior Rating Form (parent version); and on the Visual Analog Scale of the most troublesome symptom. More risperidone-treated subjects (87%) showed global improvement in their condition compared with the placebo group (40%). Somnolence, the most frequently reported adverse event, was noted in 72.5% versus 7.7% of subjects (risperidone vs placebo) and seemed manageable with dose/dose-schedule modification. Risperidone-treated subjects experienced statistically significantly greater increases in weight (2.7 vs 1.0 kg), pulse rate, and systolic blood pressure. Extrapyramidal symptoms scores were comparable between groups. CONCLUSIONS: Risperidone was well tolerated and efficacious in treating behavioral symptoms associated with PDD in children.