The effects of quinpirole in eliciting 50 kHz calls from the rat nucleus accumbens /

Fifty kHz rat vocalizations are theorized to reflect a positive affective state, and index the reward value of stimuli (Knutson, Burgdorf & Panksepp, 2002; Panksepp & Burgdorf, 2003; Brudzynski,2005). Previous studies have identified the neurochemical substrate of this behaviour to be dependent on dopaminergic activity at the nucleus accumbens shell (Burgdorf, Knutson, Panksepp & Ikemoto, 2001; Thompson, Leonard & Brudzynski, 2006). The utilization of d-amphetamine (a non-selective dopamine agonist) in these studies does not address the specific dopamine receptor types involved. The present study aims to identify the role of the D2- like family of receptors in the nucleus accumbens shell in the production of 50 kHz vocalizations in adult rats. Single injections of quinpirole in a saline vehicle were administered to the nucleus accumbens shell of 57 rats, and the number of 50 kHz vocalizations were recorded. An inverted V-shaped relationship was found between quinpirole dose (0.5 ~g, 3 ~g, 6 ~g, 1 0 ~g and 20 ~g, all in 0.2~1 saline) and the mean number of 50 kHz calls produced. Quinpirole successfully elicited significantly more 50 kHz calls than did a saline control at the 6 ~g dose, as did 7 ~g/0.2 ~l of d-amphetamine injections into the same brain site. To test whether a selective D2 antagonist could reverse elicited 50 kHz calling, double injections were given that used either saline or raclopride as a pretreatment before quinpirole injections. Saline followed by 6 ~g/0.2 ~l of quinpirole elicited significantly more 50 kHz vocalizations than did a double injection of saline, while pretreatment with an equimolar dose of raclopride reduced elicited calls to control levels. Raclopride was also used as a pretreatment of 7 ~g/0.2 ~l d-amphetamine, which elicited significantly fewer 50 kHz vocalizations than saline followed by amphetamine, replicating the finding of Thompson, Leonard & Brudzynski (2006).Subcutaneous injections of 0.5 mg/kg and 1.5 mg/kg of quinpirole produced a similar number of 50 kHz vocalizations as subcutaneous injection of saline. Wider dose ranges may be explored in fiiture research. Thus, direct activation of the Da-like receptors in the nucleus accumbens shell was sufficient to elicit 50 kHz vocalizations in adult rats, an effect which was reversed with selective local antagonism of Da-like receptors. The Da-like receptor family also appears necessary for pharmacological activation of 50 kHz calling, as d-amphetamine was no longer able to effectively elicit these vocalizations from the nucleus accumbens shell when the Da-receptor family was antagonized with raclopride. The acoustic parameters of elicited vocalizations remained typical of rat 50 kHz calls. Detailed analyses of the acoustic characteristics of elicited calls indicated significant increases in call duration and peak frequency across drug injection groups, particularly among quinpirole dose groups. The implications of these findings are not yet clear, but may represent an important direction for future research into the coding of semiotic content into affective signals in rats.

3D movement and muscle activity patterns in a violin bowing task

Objective: Overuse injuries in violinists are a problem that has been primarily analyzed through the use of questionnaires. Simultaneous 3D motion analysis and EMG to measure muscle activity has been suggested as a quantitative technique to explore this problem by identifying movement patterns and muscular demands which may predispose violinists to overuse injuries. This multi-disciplinary analysis technique has, so far, had limited use in the music world. The purpose of this study was to use it to characterize the demands of a violin bowing task. Subjects: Twelve injury-free violinists volunteered for the study. The subjects were assigned to a novice or expert group based on playing experience, as determined by questionnaire. Design and Settings: Muscle activity and movement patterns were assessed while violinists played five bowing cycles (one bowing cycle = one down-bow + one up-bow) on each string (G, D, A, E), at a pulse of 4 beats per bow and 100 beats per minute. Measurements: An upper extremity model created using coordinate data from markers placed on the right acromion process, lateral epicondyle of the humerus and ulnar styloid was used to determine minimum and maximum joint angles, ranges of motion (ROM) and angular velocities at the shoulder and elbow of the bowing arm. Muscle activity in right anterior deltoid, biceps brachii and triceps brachii was assessed during maximal voluntary contractions (MVC) and during the playing task. Data were analysed for significant differences across the strings and between experience groups. Results: Elbow flexion/extension ROM was similar across strings for both groups. Shoulder flexion/extension ROM increaslarger for the experts. Angular velocity changes mirrored changes in ROM. Deltoid was the most active of the muscles assessed (20% MVC) and displayed a pattern of constant activation to maintain shoulder abduction. Biceps and triceps were less active (4 - 12% MVC) and showed a more periodic 'on and off pattern. Novices' muscle activity was higher in all cases. Experts' muscle activity showed a consistent pattern across strings, whereas the novices were more irregular. The agonist-antagonist roles of biceps and triceps during the bowing motion were clearly defined in the expert group, but not as apparent in the novice group. Conclusions: Bowing movement appears to be controlled by the shoulder rather than the elbow as shoulder ROM changed across strings while elbow ROM remained the same. Shoulder injuries are probably due to repetition as the muscle activity required for the movement is small. Experts require a smaller amount of muscle activity to perform the movement, possibly due to more efficient muscle activation patterns as a result of practice. This quantitative multidisciplinary approach to analysing violinists' movements can contribute to fuller understanding of both playing demands and injury mechanisms .

Training distribution and the acquisition of maximal isometric elbow flexion strength

Twenty-six sedentary, college-aged females were matched and randomly assigned to one of two groups. The massed group (n=13) completed 15 maximal isometric elbow flexion strength trials in one session, while the distributed group (n=13) performed five such contractions on three successive days. After a two-week and three month rest interval, both groups returned to perfonn another five maximal isometric elbow flexion strength trials to assess retention of any potential strength gains. Elbow flexion torque and surface electromyography (SEMG) of the biceps and triceps were monitored concurrently. There was a significant (P < 0.05) increase in strength in both groups from block one (first five contractions) to block four (first retest) and from block one to block five (second retest). Both groups exhibited a similar linear increasing (P < 0.05) trend in biceps root-mean-square (RMS) SEMG amplitude. A significant (P < 0.05) decrease in triceps RMS SEMG amplitude was found between block one and block four for the distributed group. However, a significant (P < 0.05) increase was then found between block one and five for the massed group, and between blocks four and five for distributed group. These results suggest that there is flexibility in resistive exercise schedules. An increase in neural drive to the agonist muscle continued throughout testing. This was accompanied by a reduction in antagonist co activation that was a short-tenn (two weeks) training effect, dissipated over the longer rest interval (three months).

Muscle strength and activation characteristics of power- trained and non-athlete boys and men

During maturation, muscle strength is enhanced through muscle growth, although neuro-muscular factors are also believed to be involved. In adults, training for power sports has been shown to enhance muscle strength and activation. The purpose of this study was to examine muscle strength and activation in power-trained athletes (POW) compared with non-athletes (CON), in boys and in adults. After familiarization subjects performed ten 5-s explosive maximal voluntary contractions for elbow and knee flexion and extension. The adults were stronger then the boys and the adult POW were stronger then the adult CON, even after correction for muscle size. Normalized rate of torque development was higher in the adults then in the boys and higher in the POW then CON boys. The rate of muscle activation was higher in the adults and POW groups. The results suggest that maturation and power-training have an additive effect on muscle activation.

Effects of low doses of quinpirole on production of 50 kHz vocalizations in Wistar rats

Rats emit two distinct types of ultrasonic vocalizations in adulthood: 22 kHz (aversive situation), and 50 kHz calls (appetitive situation). The present project is focussed on pharmacological studies of 50 kHz vocalizations. The 50 kHz calls are elicited from dopaminergic activation in the meso limbic pathway and are emitted in such appetitive situations as social contact(s), sexual encounters, food reward, etc. Eighty-five male rats were stereotaxically implanted with bilateral guide cannulae in the nucleus accumbens shell (A= 9.7, L= 1.2, V= 6.7). Quinpirole, a D2/D3 dopaminergic agonist, was injected in low doses to the nucleus accumbens shell in an attempt to elicit 50 kHz vocalizations. A dose response was obtained for the low dose range of quinpirole for six doses: 0.025 Jlg, 0.06 Jlg, 0.12 Jlg, 0.25 Jlg, 0.5 Jlg, and 1.0 Jlg. It was found that only application of the 0.25 Jlg dose of quinpirole and the 7 Jlg dose of amphetamine (positive control) significantly increased the total number of 50 kHz calls (p < 0.006 and p < 0.004 respectively); and particularly significantly increased the frequency modulated type of these calls (p < 0.01, and p < 0.006 respectively). In a double injection procedure, the dose of 0.25 Jlg quinpirole was antagonized with raclopride (D2 antagonist) or U99194A maleate (D3 antagonist) in an attempt to antagonize the response. The 0.25 Jlg dose of quinpirole was successfully antagonized by pre-treatment with an equimolar dose of U99194A maleate (p < 0.008) but not with raclopride. The 7Jlg amphetamine response was also antagonized with an equimolar dose of raclopride. Based on these results, it seems that low doses of quinpirole, particularly the 0.25 Jlg dose, are capable of increasing 50 kHz vocalizations in rats and do so by activation of the D3 dopamine receptor. This is not a biphasic response as seen with locomotor studies. Also noteworthy is the increase in frequency modulated 50 kHz calls elicited by the 0.25 Jlg dose of quinpirole indicating a possible increase in positive affect.

Hot cognition and activation of the medial prefrontal cortex: Self-regulating in contexts involving motivational pressures

The medial prefrontal cortex (mPFC) is involved in performance-monitoring and has been implicated in the generation of several electrocortical responses associated with self-regulation. The error-related negativity (ERN), the inhibitory Nogo N2 (N2), and the feedback-related negativity (FRN) are event-related potential (ERP) components which reflect mPFC activity associated with feedback to behavioural (ERN, N2) and environmental (FRN) consequences. Our main goal was to determine whether or not rnPFC activation varies as a function of motivational context (e.g., those involving performance-related incentives) or the use of internally versus externally generated feedback signals (i.e., errors). Additionally, we assessed medial prefrontal activity in relation to individual differences in personality and temperament. Participants completed a combination of tasks in which performance-related incentives were associated with task performance and feedback generated from internal versus external responses. MPFC activity was indexed using both ERP scalp voltage peaks and intracerebral current source density (CSD) of dorsal and ventral regions. Additionally, participants completed several questionnaires assessing personality and temperament styles. Given previous studies have shown that enhanced mPFC activity to loss (or negative) feedback, we expected that activity in the mPFC would generally be greater during the Loss condition relative to the Win condition for both the ERN and N2. Also, due to the evidence that the (vmPFC) is engaged in arousing contexts, we hypothesized that activity in the ventromedial prefrontal cortex (vmPFC) would be greater than activity in the dorsomedial prefrontal cortex (dmPFC), especially in the Loss condition of the GoNogo task (ERN). Similarly, loss feedback in the BART (FRN) was expected to engage the vmPFC more than the dmPFC. Finally, we predicted that persons rating themselves as more willing to engage in approach-related behaviours or to exhibit rigid cognitive styles would show reduced activity of the mPFC. Overall, our results emphasize the role of affective evaluations of behavioural and environmental consequences when self-regulating. Although there were no effects of context on brain activity, our data indicate that, during the time of the ERN and N2 on the MW Go-Nogo task and the FRN on the BART, the vrnPFC was more active compared to the dmPFC. Moreover, regional recruitment in the mPFC was similar across internally (ERN) and externally (FRN) generated errors signals associated with loss feedback, as reflected by relatively greater activity in the vmPFC than the dmPFC. Our data also suggest that greater activity in the mPFC is associated with better inhibitory control, as reflected by both scalp and CSD measures. Additionally, deactivation of the subgenual anterior cingulate cortex (sgACC) and lower levels of self-reported positive affect were both related to increased voluntary risk-taking on the BART. Finally, persons reporting higher levels of approach-related behaviour or cognitive rigidity showed reduced activity of the mPFC. These results are in line with previous research emphasizing that affect/motivation is central to the processes reflected by mediofrontal negativities (MFNs), that the vmPFC is involved in regulating demands on motivational/affective systems, and that the underlying mechanisms driving these functions vary across both individuals and contexts.

The electromyographic threshold in children: Differences in neuromuscular activation during progressive exercise between boys and men

The electromyographic threshold (EMGTh), defined as an upward inflexion in the rising EMG signal during progressive exercise, is thought to reflect the onset of increased type-II MU recruitment. The study’s objective was to compare the relative exercise intensity at which the EMGTh occurs in boys vs. men. Participants included 21 men (23.4±4.1 yrs) and 23 boys (11.1±1.1 yrs). Ramped cycle-ergometry was conducted to volitional exhaustion with surface EMG recorded from the vastus lateralis muscles. The EMGTh was mathematically determined using a composite of both legs. EMGTh was detected in 95.2% of the men and in 78.3% of the boys (χ2(1, n=44) =2.69, p =.10). The boys’ EMGTh was significantly higher than the men’s (86.4±9.6 vs. 79.7±10.0% of peak power-output at exhaustion; p <.05). These findings suggest that boys activate their type-II MUs to a lesser extent than men during progressive exercise and support the hypothesis of differential child–adult MU activation.

Top-down and Bottom-up influences on ACC activation: Evaluation of a proposed model of the feedback-related negativity

The Feedback-Related Negativity (FRN) is thought to reflect the dopaminergic prediction error signal from the subcortical areas to the ACC (i.e., a bottom-up signal). Two studies were conducted in order to test a new model of FRN generation, which includes direct modulating influences of medial PFC (i.e., top-down signals) on the ACC at the time of the FRN. Study 1 examined the effects of one’s sense of control (top-down) and of informative cues (bottom-up) on the FRN measures. In Study 2, sense of control and instruction-based (top-down) and probability-based expectations (bottom-up) were manipulated to test the proposed model. The results suggest that any influences of medial PFC on the activity of the ACC that occur in the context of incentive tasks are not direct. The FRN was shown to be sensitive to salient stimulus characteristics. The results of this dissertation partially support the reinforcement learning theory, in that the FRN is a marker for prediction error signal from subcortical areas. However, the pattern of results outlined here suggests that prediction errors are based on salient stimulus characteristics and are not reward specific. A second goal of this dissertation was to examine whether ACC activity, measured through the FRN, is altered in individuals at-risk for problem-gambling behaviour (PG). Individuals in this group were more sensitive to the valence of the outcome in a gambling task compared to not at-risk individuals, suggesting that gambling contexts increase the sensitivity of the reward system to valence of the outcome in individuals at risk for PG. Furthermore, at-risk participants showed an increased sensitivity to reward characteristics and a decreased response to loss outcomes. This contrasts with those not at risk whose FRNs were sensitive to losses. As the results did not replicate previous research showing attenuated FRNs in pathological gamblers, it is likely that the size and time of the FRN does not change gradually with increasing risk of maladaptive behaviour. Instead, changes in ACC activity reflected by the FRN in general can be observed only after behaviour becomes clinically maladaptive or through comparison between different types of gain/loss outcomes.

The time-course of lexical activation in Japanese morphographic word recognition: Evidence for a character-driven processing model

This lexical decision study with eye tracking of Japanese two-kanji-character words investigated the order in which a whole two-character word and its morphographic constituents are activated in the course of lexical access, the relative contributions of the left and the right characters in lexical decision, the depth to which semantic radicals are processed, and how nonlinguistic factors affect lexical processes. Mixed-effects regression analyses of response times and subgaze durations (i.e., first-pass fixation time spent on each of the two characters) revealed joint contributions of morphographic units at all levels of the linguistic structure with the magnitude and the direction of the lexical effects modulated by readers’ locus of attention in a left-to-right preferred processing path. During the early time frame, character effects were larger in magnitude and more robust than radical and whole-word effects, regardless of the font size and the type of nonwords. Extending previous radical-based and character-based models, we propose a task/decision-sensitive character-driven processing model with a level-skipping assumption: Connections from the feature level bypass the lower radical level and link up directly to the higher character level.