<p> Behavioral sensitization is an increase in a behavioral response (e.g., locomotor activity or stereotypy) induced by previous drug exposure. The present study examined one-trial methamphetamine behavioral sensitization in male and female rats during early or late adolescence. During pretreatment, male and female rats received methamphetamine (0.0&ndash;6.0 mg/kg) in the home or in a novel chamber during early (PD 38) or late (PD 48) adolescence. After 24 hours, rats received a 1 mg/kg methamphetamine challenge test dose in the novel chamber to assess for sensitization. The results showed that rats in both age groups exhibited robust locomotor activity to the acute effects of methamphetamine. However, male and female rats at either age group did not exhibit one-trial methamphetamine behavioral sensitization. Overall, females exhibited greater locomotor activity than males, while males exhibited greater stereotypy. These findings do not provide evidence that the ontogeny of one-trial methamphetamine sensitization emerges during adolescence.</p>

<p> Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are two debilitating and relatively common early-onset neurodegenerative disorders along a clinicopathologic spectrum. Accounting for ~25% of familial FTD and ~30% of familial ALS, a GGGGCC hexanucleotide repeat expansion in chromosome 9 open reading-frame 72 (C9ORF72) is the most common known genetic cause of both disorders (c9FTD/ALS). While many neuropathologic features of c9FTD/ALS cases mirror archetypal FTD/ALS [i.e., focal neuronal loss, TAR DNA-binding protein 43 (TDP-43) pathology, etc.], a subset of neuronal lesions have been observed which are positive for ubiquitin, but negative for TDP-43, suggesting additional underlying pathology. Our goal of this study was to eliminate the possibility of the involvement other classic neurodegenerative protein (tau and amyloid-&beta;) and identify novel aggregating proteins which could potentially serve as biomarkers and therapeutic targets. Using quantitative neuropathologic assessment, we demonstrated tau and amyloid-&beta; did not consistently co-localize with these ubiquitinated inclusions and was not more common in c9FTD/ALS compared to sporadic FTD and ALS cases (as well as FTD cases with another known mutation, GRN). Following insights from the field of trinucleotide repeat disorders, we discovered novel pathologic dipeptide repeats in c9FTD/ALS generated through the process of repeat-associated non-ATG (RAN) translation. These dipeptide repeat proteins had a very characteristic and consistent morphology, distribution, and pathologic burden amongst c9FTD/ALS cases. These proteins were also highly specific to C9ORF72 repeat expansion carriers, even in clinically and neuropathologically atypical cases. Subsequent research from this initial finding has not only confirmed our results, but also demonstrated the toxicity of these proteins and even their therapeutic potential towards ameliorating disease in individuals harboring the C9ORF72 expansion.</p>

<p> Purpose: Non-verbal cognition and language functions were examined in adult stroke survivors with aphasia. The specific purpose of the study was twofold: 1) to examine the relationship between self-reported outcomes from people with aphasia (PwA), measures of non-verbal cognition (Delis-Kaplan Executive Function Systems Test (D-KEFS), Delis, Kaplan, &amp; Kramer, 2001) and measures of language (Western Aphasia Battery-Revised (WAB-R), Kertesz, 2007; Boston Naming Test Second Edition (BNT-2), Kaplan, Goodglass, &amp; Weintraub, 2001) and 2) to examine these same relationships using partner-reported outcomes for that same group of PwA. This study used the Aphasia Communication Outcome Measure (ACOM, Doyle et al., 2013) to gather both self-reported ACOM data and partner-reported ACOM data (ratings of the person with aphasia&rsquo;s communication made by a regular conversation partner). </p><p> Method: Seventeen participants with aphasia underwent examination with an extensive test battery including measures of functional communication, non-verbal cognition, and language impairment. In addition, 16 of their regular communication partners rated functional communication performance. </p><p> Results: Self-reported functional communication is strongly related to the number of errors committed on the D-KEFS design fluency test (r = .81, p = .001). Furthermore, a modified form of the D-KEFS design fluency test (in which the examinee is allowed unlimited time) shows that the proportion of errors contributes significantly to a two- predictor linear regression model. These two predictors account for 66% of the variance in self-reported functional communication ratings. These results suggest that non-verbal cognition for people with mild to moderate aphasia may serve an important role in functional communication. By contrast, self-reported functional communication was uncorrelated with aphasia severity (r = .04, p = .88), naming performance on either the WAB-R (r=.059, p=.823) or the BNT-2 (r=.097, p=.713), and category fluency (r=.086, p=.741). Partner-reported functional communication was highly correlated to the naming subtest on Western Aphasia Battery-Revised (WAB-R) scores (r=.71, p=.02) and to performance on the Boston Naming Test (BNT-2; r=.56, p=.026). </p><p> Partner-reported functional communication was also strongly predicted based on the number of animals named during the category fluency task on the WAB-R (r=.782, p=.000). A linear regression model including WAB-R category fluency accounted for 61.1% of the variance in partner-reported ratings. A second linear regression adding naming as a predictor was not significant (F_change = 2.18, p=.163). By contrast, none of the non-verbal cognition measures were useful predictors of partner-reported functional communication. These results suggest that aphasia severity serves an important role in partner ratings of functional communication whereas non-verbal cognition does not. </p><p> Taken together, these results suggest that PwA and their partners rely on different aspects of communication when judging functional communication. </p><p> Further work to explore the use of patient-reported outcome (PRO) measures and to identify factors that contribute to self-reported functional communication is needed. The discussion addresses the appropriateness of using PRO measures in aphasia and the use of surrogate reports.</p>

<p> <b><u>Objective:</u></b> This is a pilot study designed to assess speech and swallowing characteristics of participants with idiopathic Parkinson&rsquo;s disease (IPD) before deep brain stimulation surgery of the subthalamic nucleus (DBS-STN), after the DBS-STN surgery, and at follow up evaluation sessions.</p><p> <b><u>Method:</u></b> A within participant, single-subject experimental A-B-A-A design was used to measure changes in the dependent variables for each participant. The primary dependent variables were intelligibility scores of words and sentences, vowel space area (VSA), vocal sound pressure level (dB SPL) of sustained vowels, single words, and contextual speech, Multidimensional voice program (MDVP) analysis of phonatory stability of sustained vowel phonation, lip pressure, tongue tip to alveolar ridge pressure, maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and diadochokinetic rate. The secondary dependent variables were: duration of sustained vowel phonation, Visual analog scales (VAS) for communicative difficulties and swallowing difficulties, the EAT-10 swallowing questionnaire, and the qualitative narrative of life with IPD before and after the DBS-STN surgery.</p><p> <b><u>Results:</u></b> DBS-01 had significant declines of intelligibility with individual words, but did not have statistically significant changes for complete sentences. The VSA declined over the course of the study. The MDVP analyses indicated general declines in phonatory stability, but not significantly. There was a statistically significant increase in dB SPL for sustained vowel phonation, but there were overall declines in loudness for connected speech. The duration of sustained vowel phonation increased and the DDK rate varied across the experiment. Left lip and tongue pressures had overall declines, but right and center lip pressures increased. The VAS for communicative difficulties revealed worsening of symptoms. The VAS and the EAT-10 questionnaire for swallowing difficulties both recorded worsening of symptoms after surgery, and symptom improvements later on. The timed swallow test did not show any meaningful impairment in drinking or eating.</p><p> DBS-02 had statistically significant gains of intelligibility with individual words after the DBS-STN surgery, but had statistically significantly declines later on. The changes in the intelligibility of complete sentences were not significant. The VSA contracted after the surgery, but it increased afterwards. The MDVP analyses indicated an overall significant increase of phonatory stability. The dB SPL had a statistically significant increase for sustained vowel phonation, but the connected speech loudness had mixed results. The duration of sustained vowel phonation increased after surgery, but then declined later on. The DDK rate varied across the experiment. Lip and tongue pressures had overall increases. The VAS for communication difficulties revealed an overall increase in communicative abilities. The VAS and the EAT-10 questionnaire for swallowing difficulties both recorded a decrease in symptoms after surgery, and an increase later on. The timed swallow test did not show any meaningful impairment in drinking or eating.</p><p> <b><u>Conclusions:</u></b> DBS-01 had an overall result that the DBS-STN surgery and electrode adjustments were not apparently beneficial to speech and swallowing symptoms, although the delay in assessment after the surgery made distinguishing the effects of the surgery from progressive IPD symptoms difficult. DBS-02 had an overall result that the DBS-STN surgery was beneficial to speech and swallowing symptoms in the short term, although later progression of IPD symptoms, as well as electrode adjustments likely caused later declines.</p>

Some experiences occurring early in life affect structure and function of the nervous system. Handling and isolation of infant rats produce physiological and behavioral changes that persist throughout life. These changes may result from interference with the maturation of late developing systems, such as the hippocampus. The research reported here used handling and isolation alone, and in combination, and measured activity, cognitive ability and plasma CORT levels in adult rats. Handling resulted in increased activity, decreased CORT levels, and impaired spatial learning ability. Isolation failed to alter activity levels, impaired spatial ability, and increased CORT levels in females, and reduced them in males. Combining the two manipulations produced no changes in behavior or CORT levels. The results are discussed in terms of altering the manner in which the animals respond to environmental challenges.

<p> Attention deficit hyperactivity disorder (ADHD) is one of the most challenging children&rsquo;s public health concerns today. Children diagnosed with ADHD struggle more academically and are at a significant risk of lower academic achievement, increased grade-level retention, and additional diagnoses of learning disabilities. Symptoms of ADHD primarily arise from deficits in specific executive function (EF) domains, one of which is working memory (WM). Children diagnosed are impaired on tasks that specifically measure WM capacity and short-term visuo-spatial memory. In this study, four fifth-grade students diagnosed with ADHD were administered a variety of assessments. WM was measured through a math vocabulary recall, visuo-spatial WM via a computerized Corsi Block Tapping Test, and WM capacity was assessed through an Operation Span Task. In addition, on-task behavior was determined using the partial interval recording process with overall mathematical skill based knowledge being evaluated through a pre and post assessment. Using the ABAB Withdrawal Single-Case Research Design, a 10-min intervention of short burst high intensity exercise was introduced. Participants were assessed each session (daily) and exhibited improvement on all measurements during the intervention conditions of the study. </p><p> The results suggest that a vigorous 10-min daily regime of short-burst-high-intensity exercise improves the working memory and on-task behavior of preadolescent children diagnosed with ADHD.</p>

<p> Engaging, maintaining, and treating patients with anorexia nervosa (AN) remains a significant challenge for clinicians, hypothesized explanations for which are thought to involve specific executive functioning impairments. The neuropsychological treatment paradigm Cognitive Remediation Therapy (CRT) represents the translation of neurocognitive research into practice, and is thought to remediate neuropsychological symptoms and associated maladaptive cognitive processes. Additionally, the etiological model of AN related to executive functioning provides a conceptual framework for this novel approach to treatment. This study identifies and examines such a model, in addition to CRT protocols. Methodology involved a comprehensive synthesis and critical analysis of the literature pertaining to these domains. A variety of promising findings attributed to CRT are discussed, including an increase in participant BMI, improved neuropsychological performance, reduced perseveration, increased capacity for global processing, decreased eating disorder and depressive symptomatology, increased motivation, and confidence in patients&rsquo; ability to change and begin subsequent therapies. Numerous important methodological limitations are also elucidated, as many studies utilized small sample sizes resulting in low statistical power and poor generalizability, neglected to identify or consider demographic and cultural variables, failed to assess general intelligence or reference the normative data used, did not identify or discuss potential cohort or practice effects, provided limited details influencing studies&rsquo; reproducibility, and introduced a variety of biases. Nevertheless, this groundwork illuminated promising results in the treatment of a diagnostically complex and challenging disorder. Accordingly, a number of suggested future directions and clinical applications are elaborated upon.</p>

<p> Most people choose to listen to music that they prefer or like such as classical, country or rock. Previous research has focused on how different characteristics of music (i.e., classical versus country) affect the brain. Yet, when listening to preferred music regardless of the type&mdash;people report they often experience personal thoughts and memories. To date, understanding how this occurs in the brain has remained elusive. Using network science methods, I evaluated differences in functional brain connectivity when individuals listened to complete songs. Here the results reveal that a circuit important for internally focused thoughts, known as the default mode network, was most connected when listening to preferred music. The results also reveal that listening to a favorite song alters the connectivity between auditory brain areas and the hippocampus, a region responsible for memory and social emotion consolidation. Given that musical preferences are uniquely individualized phenomena and that music can vary in acoustic complexity and the presence or absence of lyrics, the consistency of these results was contrary to previous neuroscientific understanding. These findings may explain why comparable emotional and mental states can be experienced by people listening to music that differs as widely as Beethoven and Eminem. The neurobiological and neurorehabilitation implications of these results are discussed.</p>

The aims of this research were: (1) to examine the effect of subtle changes in the stimulation pattern on the fatigability (force decline) of single motor units during repetitive activation; and (2) to determine the relationship between the magnitude of submaximal force developed and the subsequent fatigue within these units. The experiments were performed on motor units of the tibialis posterior muscle in deeply anesthetized cats. Preliminary experiments revealed that fast-twitch motor units remained fatigued for several hours following short periods of repetitive stimulation, such that sequential testing of a single motor unit with different stimulation protocols was not feasible. Hence, a new fatigue test was developed to compare the effects of two stimulation patterns during fatigue. Two different stimulation patterns were pseudo-randomly delivered at 1 train/second for 360 seconds to single motor axons. One pattern (regular) was composed of a 500-millisecond duration train with constant interpulse intervals customized to the twitch contraction time of each unit (stimulus interval range, 27-51 ms). The other pattern (optimized) was designed to increase the amount of force produced in the control (pre-fatigue) state. It consisted of three initial stimuli with short (10 ms) interpulse intervals, followed by a constant-interpulse interval train that was adjusted to have the same number of pulses and duration as the regular train (stimulus interval range, 29-62 ms). The force elicited during the fatigue test was decomposed to reveal a force profile attributable to each stimulation pattern. The results showed that the optimized pattern produced significantly more force during both control and fatiguing contractions. This suggested that force optimization is a potential mechanism by which the CNS might counteract fatigue. The association between the magnitude or submaximal force produced by an individual motor unit and its subsequent fatigue was tested within the same population of units. The results showed that the increased force due to optimized stimulation was associated with decreased fatigue, and that the cumulative force produced during fatiguing contractions could be predicted from the units' pre-fatigue force. It is concluded that an inverse relationship between force and fatigability does not exist at the level of the individual motor unit under these conditions. Rather, the results showed that the amount of force a unit can develop over time during fatiguing contractions is dependent, in part, on the pattern of stimulation.

The discovery of endogenous opioid peptides and multiple opioid receptors may lead to a new avenue in understanding the mechanisms of opioid action and treatment of pain. The specific aims of the present study are to determine whether (1) subtypes of the opioid δ receptor exist; (2) if antinociceptive efficacy of μ agonists is modulated by δ agonists; and (3) if development of morphine tolerance and dependence is reduced by co-administration of μ and δ agonists producing equivalent antinociception to that achieved with μ agonists alone. The antinociceptive effect of opioid agonists was measured using warm water mouse tail flick assay. Intracerebroventricular (i.c.v. administration of the δ agonists, (D-Pen², D-Pen⁵) enkephalin (DPDPE), (D-Ser², Leu⁵, Thr⁶) enkephalin (DSLET), (D-Ala², Leu⁵, Cys⁶) enkephalin (DALCE), or deltorphin II produced antinociceptive effects, which were blocked by the δ antagonist ICI 174,864. Following pretreatment, DALCE also produced antagonism of DPDPE and DALCE, but not deltorphin II and DSLET induced antinociception. The antinociceptive effects of DSLET and deltorphin II, but not of DPDPE and DALCE, were antagonized by naltrindole-5'-isothiocyanate (5'-NTII), a δ antagonist. Sub-antinociceptive doses of DPDPE, DSLET, and deltorphin II positively modulated morphine antinociception. The modulation was blocked by ICI 174,864 or 5'-NTII. DALCE produced neither modulation of morphine antinociception as a δ agonist, nor antagonism of the modulatory effects of DPDPE, DSLET, and deltorphin II as a δ antagonist. Under conditions of high stimulus intensity, morphine acted as a partial agonist; morphine efficacy was increased to the level of a full agonist in the presence of sub-antinociceptive doses of δ agonists, such as (Leu⁵) enkephalin, DPDPE, or the neutral endopeptidase inhibitor, thiorphan. Again, these modulatory effects were antagonized by i.c.v. ICI 174,864. In the presence of sub-antinociceptive dose of DPDPE or (Leu⁵) enkephalin, morphine produced antinociception equivalent to that of a higher dose of morphine, and antinociceptive tolerance and dependence developed more slowly. These data demonstrate the existence of subtypes of δ receptor, i.e., DALCE sensitive and 5'-NTII sensitive δ receptors. In addition, morphine antinociception can be positively modulated by δ agonists without increasing the rate of development of antinociceptive tolerance and physical dependence.