Mixed Amphetamine Salts Without a Mood Stabilizer for Treating Comorbid Attention-Deficit Hyperactivity Disorder and Bipolar Disorder: Two Case Reports.

Attention-deficit hyperactivity disorder (ADHD) and bipolar disorder (BD) are often comorbid in patients and can have significant overlap in symptoms. Because of this common comorbidity and often overlapping symptoms, accurate diagnoses can be difficult. The standard treatment for these comorbid disorders is a mood stabilizer with the possibility of adding a psychostimulant. However, research suggesting treatment for comorbid disorders with a psychostimulant without a mood stabilizer is lacking. Here, we present two cases where mixed amphetamine salts, which are traditionally avoided in those with BD, were effectively used without a mood stabilizer to treat comorbid BD and ADHD in both patients. The outcome of this case series serves to motivate future investigations which are needed to validate treatment with a psychostimulant without a mood stabilizer for the treatment of comorbid BD and ADHD.

Effects of Spectral Envelope and Fundamental Frequency Shifts on the Perception of Foreign-Accented Speech.

To investigate the role of spectral pattern information in the perception of foreign-accented speech, we measured the effects of spectral shifts on judgments of talker discrimination, perceived naturalness, and intelligibility when listening to Mandarin-accented English and native-accented English sentences. In separate conditions, the spectral envelope and fundamental frequency (F0) contours were shifted up or down in three steps using coordinated scale factors (multiples of 8% and 30%, respectively). Experiment 1 showed that listeners perceive spectrally shifted sentences as coming from a different talker for both native-accented and foreign-accented speech. Experiment 2 demonstrated that downward shifts applied to male talkers and the largest upward shifts applied to all talkers reduced the perceived naturalness, regardless of accent. Overall, listeners rated foreign-accented speech as sounding less natural even for unshifted speech. In Experiment 3, introducing spectral shifts further lowered the intelligibility of foreign-accented speech. When speech from the same foreign-accented talker was shifted to simulate five different talkers, increased exposure failed to produce an improvement in intelligibility scores, similar to the pattern observed when listeners actually heard five foreign-accented talkers. Intelligibility of spectrally shifted native-accented speech was near ceiling performance initially, and no further improvement or decrement was observed. These experiments suggest a mechanism that utilizes spectral envelope and F0 cues in a talker-dependent manner to support the perception of foreign-accented speech.

Unsupervised repetition enables rapid perceptual learning.

This study examined how listeners disambiguate an auditory scene comprising multiple competing unknown sources and determine a salient source. Experiment 1 replicated findings from McDermott, Wrobleski, and Oxenham. [(2011). Proc. Natl. Acad. Sci. U. S. A. 108(3), 1188-1193] using a multivariate Gaussian model to generate mixtures of two novel sounds. The results showed that listeners were unable to identify either sound in the mixture despite repeated exposure unless one sound was repeated several times while being mixed with a different distractor each time. The results support the idea that repetition provides a basis for segregating a single source from competing novel sounds. In subsequent experiments, the previous identification task was extended to a recognition task and the results were modeled. To confirm the repetition benefit, experiment 2 asked listeners to recognize a temporal ramp in either a repeating sound or non-repeating sounds. The results showed that perceptual salience of the repeating sound allowed robust recognition of its temporal ramp, whereas similar features were ignored in the non-repeating sounds. The response from two neural models of learning, generalized Hebbian learning and anti-Hebbian learning, were compared with the human listener results from experiment 2. The Hebbian network showed a similar response pattern as for the listener results, whereas the opposite pattern was observed for the anti-Hebbian output.

Task-dependent effects of nicotine treatment on auditory performance in young-adult and elderly human nonsmokers.

Electrophysiological studies show that nicotine enhances neural responses to characteristic frequency stimuli. Previous behavioral studies partially corroborate these findings in young adults, showing that nicotine selectively enhances auditory processing in difficult listening conditions. The present work extended previous work to include both young and older adults and assessed the nicotine effect on sound frequency and intensity discrimination. Hypotheses were that nicotine improves auditory performance and that the degree of improvement is inversely proportional to baseline performance. Young (19-23 years old) normal-hearing nonsmokers and elderly (61-80) nonsmokers with normal hearing between 500 and 2000 Hz received nicotine gum (6 mg) or placebo gum in a single-blind, randomized crossover design. Participants performed three experiments (frequency discrimination, frequency modulation identification, and intensity discrimination) before and after treatment. The perceptual differences were analyzed between pre- and post-treatment, as well as between post-treatment nicotine and placebo conditions as a function of pre-treatment baseline performance. Compared to pre-treatment performance, nicotine significantly improved frequency discrimination. Compared to placebo, nicotine significantly improved performance for intensity discrimination, and the improvement was more pronounced in the elderly with lower baseline performance. Nicotine had no effect on frequency modulation identification. Nicotine effects are task-dependent, reflecting possible interplays of subjects, tasks and neural mechanisms.

Rapid adaptation to non-native speech is impaired in cochlear implant users.

To examine difficulties experienced by cochlear implant (CI) users when perceiving non-native speech, intelligibility of non-native speech was compared in conditions with single and multiple alternating talkers. Compared to listeners with normal hearing, no rapid talker-dependent adaptation was observed and performance was approximately 40% lower for CI users following increased exposure in both talker conditions. Results suggest that lower performance for CI users may stem from combined effects of limited spectral resolution, which diminishes perceptible differences across accents, and limited access to talker-specific acoustic features of speech, which reduces the ability to adapt to non-native speech in a talker-dependent manner.

A Preliminary Investigation on the Effects of Atenolol for Treating Symptoms of Anxiety.

INTRODUCTION: Anxiety disorders are among the most commonly diagnosed of psychiatric disorders. Many symptoms of posttraumatic stress disorder are also anxiety-related. Traditional medications used to treat these disorders, such as antidepressants and benzodiazepines, are often ineffective, not well-tolerated, and can be habit forming. An alternative agent is, therefore, needed. Beta-blockers are one class of medication with potential to treat anxiety-related disorders; however, current evidence remains limited and requires further characterization. To this end, this retrospective study aims to present a novel preliminary report on the use of the beta-blocker, atenolol, to potentially treat anxiety-related disorders. MATERIALS AND METHODS: Ninety-two patients were identified from outpatient military mental health clinics in Okinawa, Japan, who had received atenolol for mental health-related symptoms. Primary measures collected were the rates of patient-reported (1) general beneficial/positive effect of atenolol, (2) adverse effects from atenolol, and (3) preference of atenolol to propranolol. Data were collected from patients who were given binary response options to report their perceived experiences for each primary measure. This study was approved by the Naval Medical Center San Diego Institutional Review Board. RESULTS: The results showed 86% of patients reporting a positive effect and continuing to take atenolol, including 87% with a diagnosis of posttraumatic stress disorder, 100% with diagnosis of other specified trauma- and stressor-related disorder, and 81% diagnosed with anxiety disorders. In total, 90% of patients denied adverse effects or found the adverse effects tolerable. Additionally, 100% of patients who had previously taken propranolol for anxiety reported that they preferred atenolol. CONCLUSIONS: The present preliminary observational data suggests that atenolol may be well-tolerated and effective among persons with anxiety disorders. These data also suggest that atenolol may be more effective and better tolerated than propranolol, which is the most commonly prescribed beta-blocker for these conditions; however, more rigorously controlled empirical studies are needed to further substantiate this claim. Despite an overwhelmingly high rate of positive reports from patients' self-evaluations of atenolol treatment for anxiety-related disorders, this early investigation was not placebo-controlled nor double-blinded, and formal outcome measures were not assessed due to a lack of availability. More detailed examinations are needed to further determine whether atenolol is a viable alternative or augmenting agent to propranolol, benzodiazepines, and antidepressants for anxiety disorders and trauma-related disorders.

Interventional Study of Dextromethorphan Abuse Within the U.S. Military Community in Okinawa, Japan.

Dextromethorphan, a common over-the-counter cough suppressant, has potential for abuse. In the present commentary, we summarize findings to suggest extensive dextromethorphan overuse/abuse within the U.S. military community residing in Okinawa, Japan. We first compared sales of dextromethorphan-containing medications within the U.S. military community of Okinawa, Japan with sales within the U.S military community from the other nearby locations in the Pacific region. Our report revealed that dextromethorphan use is far more prevalent within the military community in Okinawa. To further substantiate the claim that dextromethorphan abuse is widespread in Okinawa's U.S. military community, a survey of medical records showed high rates of treatment provided for dextromethorphan intoxication. These findings motivated interventions established throughout the military community in Okinawa to combat dextromethorphan overuse. These stricter policy changes resulted in decreases in sales of dextromethorphan-containing medications as well as a substantial drop in hospital visits from dextromethorphan intoxication, suggesting that the interventions were largely effective and should be maintained.

Nicotine enhances auditory processing in healthy and normal-hearing young adult nonsmokers.

RATIONALE: Electrophysiological studies show that systemic nicotine narrows frequency receptive fields and increases gain in neural responses to characteristic frequency stimuli. We postulated that nicotine enhances related auditory processing in humans. OBJECTIVES: The main hypothesis was that nicotine improves auditory performance. A secondary hypothesis was that the degree of nicotine-induced improvement depends on the individual's baseline performance. METHODS: Young (18-27 years old), normal-hearing nonsmokers received nicotine (Nicorette gum, 6mg) or placebo gum in a single-blind, randomized, crossover design. Subjects performed four experiments involving tone-in-noise detection, temporal gap detection, spectral ripple discrimination, and selective auditory attention before and after treatment. The perceptual differences between posttreatment nicotine and placebo conditions were measured and analyzed as a function of the pre-treatment baseline performance. RESULTS: Nicotine significantly improved performance in the more difficult tasks of tone-in-noise detection and selective attention (effect size = - 0.3) but had no effect on relatively easier tasks of temporal gap detection and spectral ripple discrimination. The two tasks showing significant nicotine effects further showed no baseline-dependent improvement. CONCLUSIONS: Nicotine improves auditory performance in difficult listening situations. The present results support future investigation of nicotine effects in clinical populations with auditory processing deficits or reduced cholinergic activation.

Plasticity in Limbic Regions at Early Time Points in Experimental Models of Tinnitus.

Tinnitus is one of the most prevalent auditory disorders worldwide, manifesting in both chronic and acute forms. The pathology of tinnitus has been mechanistically linked to induction of harmful neural plasticity stemming from traumatic noise exposure, exposure to ototoxic medications, input deprivation from age-related hearing loss, and in response to injuries or disorders damaging the conductive apparatus of the ears, the cochlear hair cells, the ganglionic cells of the VIIIth cranial nerve, or neurons of the classical auditory pathway which link the cochlear nuclei through the inferior colliculi and medial geniculate nuclei to auditory cortices. Research attempting to more specifically characterize the neural plasticity occurring in tinnitus have used a wide range of techniques, experimental paradigms, and sampled at different windows of time to reach different conclusions about why and which specific brain regions are crucial in the induction or ongoing maintenance of tinnitus-related plasticity. Despite differences in experimental methodologies, evidence reveals similar findings that strongly suggest that immediate and prolonged activation of non-classical auditory structures (i.e., amygdala, hippocampus, and cingulate cortex) may contribute to the initiation and development of tinnitus in addition to the ongoing maintenance of this devastating condition. The overarching focus of this review, therefore, is to highlight findings from the field supporting the hypothesis that abnormal early activation of non-classical sensory limbic regions are involved in tinnitus induction, with activation of these regions continuing to occur at different temporal stages. Since initial/early stages of tinnitus are difficult to control and to quantify in human clinical populations, a number of different animal paradigms have been developed and assessed in experimental investigations. Reviews of traumatic noise exposure and ototoxic doses of sodium salicylate, the most prevalently used animal models to induce experimental tinnitus, indicate early limbic system plasticity (within hours, minutes, or days after initial insult), supports subsequent plasticity in other auditory regions, and contributes to the pathophysiology of tinnitus. Understanding this early plasticity presents additional opportunities for intervention to reduce or eliminate tinnitus from the human condition.

Perceiving foreign-accented speech with decreased spectral resolution in single- and multiple-talker conditions.

To determine the effect of reduced spectral resolution on the intelligibility of foreign-accented speech, vocoder-processed sentences from native and Mandarin-accented English talkers were presented to listeners in single- and multiple-talker conditions. Reduced spectral resolution had little effect on native speech but lowered performance for foreign-accented speech, with a further decrease in multiple-talker conditions. Following the initial exposure, foreign-accented speech with reduced spectral resolution was less intelligible than unprocessed speech in both single- and multiple-talker conditions. Intelligibility improved with extended exposure, but only for single-talker conditions. Results indicate a perceptual impairment when perceiving foreign-accented speech with reduced spectral resolution.