The adage practice makes perfect makes for sound advice when learning a novel motor skill. Be it typing a new password or hitting a forehand in tennis, proficiency increases with experience. Behavioral changes associated with motor skill acquisition can be broken down into three broad categories: (1) movements are executed faster and become more coordinated, (2) they come to rely on sensory information gained while executing the task, rather than just sensory information used during initial stages of learning the task, and (3) they seem to be executed with less conscious thought and attention. In addition, neural activity changes: many imaging and neural recording studies suggest that with experience, control is transferred from cortical planning areas to the basal ganglia. The two areas are thought to employ different learning and control schemes. In general, planning can quickly take new information into account to make reasonable decisions, but its control mechanisms have large computational requirements. The basal ganglia use a simpler and less computationally expensive control scheme, but they require much experience before they can produce reasonable behavior. In this thesis, I contribute to answering the question, "what goes on during practice?" More formally, I am interested in the mechanisms by which motor skills are acquired. I take a theoretical approach in that I hypothesize a multiple controller scheme, based on the learning and control mechanisms of cortical planning areas and the basal ganglia, and test it with simulations designed emulate generic motor skill tasks. Because skill proficiency increases with experience, I am particularly interested in the role of the experience-dependent mechanisms of the basal ganglia in motor skill acquisition. Thus, learning mechanisms attributed to cortical areas are artificially restricted so that any change in model behavior is attributed to the learning mechanisms of the basal ganglia. Model behaviors exhibit characteristics indicative of motor skills, supporting the plausibility of the multiple controller scheme as one used by our nervous system and suggesting that the learning mechanisms of the basal ganglia can contribute to developing most characteristics. In addition, I show how the strategies developed by the models are functionally advantageous, providing a reason why such a scheme may be used.

Findings from various studies investigating treatment of severe addictions lead to the conclusion that coping skills training in group therapy is viable and addresses both the vulnerabilities and capacities of addicts. This study adapted coping skills training as treatment for use in groups, on cocaine using clients in a methadone maintenance treatment program. The customary education format was used in a control group and the effects on outcome of both treatments were analyzed. The groups were conducted in the methadone clinic. The participants were 46 clients admitted to the methadone treatment program, abusing and or dependent on cocaine. They all volunteered to participate in the study. Subjects who volunteered to be in the experimental group had no time constraints, no transportation problems and were all unemployed. Clients identified high-risk situations in which they would use cocaine and coping skills training modules were selected to address these specific needs.

Gonadal steroid hormones play an important role in central nervous system development, including brain areas associated with cognition. High levels of progestin binding and progestin receptor (PR) mRNA have been reported in developing cortex, at around the time when the cortex synthesizes high levels of progesterone de novo. Peak levels of PR expression are concurrent with many major growth processes, such as peak dendritic spine and afferent synapse formation in cortical neurons. We used the cellular-level resolution of immunohistochemistry to characterize changes in PR expression within specific cortical lamina over the course of development. The results indicate that PR immunoreactivity (PR-ir) is transiently expressed in specific lamina of frontal, parietal, temporal and occipital cortex. Beginning on E18, PR-ir was observed in subplate cells and then in increasingly superficial lamina (primarily lamina V, then II/III) as postnatal development continued through P13. By P27, this pattern of PR-ir was absent. Double labeling with specific antibodies indicated that PR-ir colocalized with microtubule associated protein (MAP)-2, a neuronal marker, but not with the glial marker, nestin, nor with GABA-ir, suggesting that PR is primarily expressed in excitatory neurons. We also examined whether PR function alters dendritic branching and spine formation on developing cortical cells. Rat pups were subcutaneously injected with the PR antagonist RU486 or oil daily and then sacrificed on P6, P11 or P14. Immunohistochemistry and Western immunoblots were used to measure the levels of synaptic (synaptophysin, syntaxin, spinophilin) and dendritic protein (MAP-2). No differences were found between RU486 and vehicle treated pups in any brain areas examined. These results suggest that specific subpopulations of cortical neurons may be transiently sensitive to progesterone, and that progesterone and its receptor may play a critical role in the fundamental mechanisms underlying normal cortical perinatal development. However, PR influence on perinatal development may exclude effects on cortical synaptogenesis and dendrite formation.

Purpose. The aim of this investigation was: (i) to examine age-related differences in maximal motor unit firing rates, cortical excitability and inhibition, spinal excitability and inhibition, and motoneuron afterhyperpolarization (AHP) duration, in the tibialis anterior; (ii) to examine which of these factors limit maximal motor unit firing rates in young and older adults; and (iii) to determine if these factors are adaptable in young and older males and females, in response to resistance training. A host of neuromuscular measures were made from young and older subjects before and after a 2-week isometric resistance training protocol. Methods. Sixty subjects, 30 young (mean age 21.9±3.1 years) and 30 older (mean age 72.9±4.6 years) individuals were tested. Fifteen subjects from each age group were randomly assigned to either a control or training group. All subjects underwent baseline testing, including measures of: maximal voluntary contraction (MVC) force of the dorsiflexors, central activation, maximal motor unit firing rates, duration of the motoneuron AHP, cortical excitability and inhibition, spinal excitability and presynaptic and reciprocal inhibition. The control group was then asked to carry out their normal daily activities for two weeks, and the training group participated in isometric training of the dorsiflexors. Training consisted of three sets of ten 5-second MVCs, three times per week, for two weeks. Following the two-week period, all subjects returned to the laboratory for reassessment of the baseline measures. During testing sessions, a needle electrode was inserted into the tibialis anterior (TA) to monitor muscle activity while subjects perform 3 maximal voluntary contractions, each lasting 5 s. Subjects also performed 3 contractions, at approximately 2% MVC, each held for approximately 7-8 minutes, and the duration of the motoneuron AHP was estimated from the motor unit firings. Spinal excitability was assessed with the slope of the ascending limb of the stimulus-response curve of the TA H-reflex, evoked at various stimulus intensities. Presynaptic and reciprocal inhibition were assessed by conditioning the TA H-reflex with a stimulus applied to the tibial nerve. The slope of the ascending limb of the TA motor-evoked potential (MEP) stimulus-response curve was used as an indication of cortical excitability. MEPs were also evoked while subjects perform isometric dorsiflexion to 50% MVC, and the duration of the silent period was used as an indication of cortical inhibition. Results. Young subjects had a higher MVC force, central activation ratio, maximal motor unit firing rate, spinal excitability and cortical excitability than older subjects. Older subjects also had longer duration AHP time constants, and shorter duration cortical silent periods than young subjects. The only gender differences observed were higher MVC force and higher maximal motor unit firing rates in males compared to females. Isometric strength training of the dorsiflexors resulted in increases in MVC force and maximal motor unit firing rate, and decreases in the AHP time constant and presynaptic inhibition. With respect to predictors of maximal motor unit firing rate, the baseline data suggested that, of all of the neuromuscular measures, presynaptic inhibition was the best predictor of maximal firing rate. The change in the maximal motor unit firing rate from Day 1 to Day 2, however, was best predicted by changes in presynaptic inhibition and changes in the duration of the AHP time constant. Conclusions. The results of this study suggest significant age-related changes in the ability to produce force, maximal motor unit firing rates, and associated changes at multiple levels of the neuromuscular system. Many of the neuromuscular measures, however, showed changes in response to isometric strength training in both young and older adults. These results suggest that there is some plasticity in the neuromuscular system, regardless of age. The regression analysis suggests that the properties of the motoneurons, as well as the level of spinal inhibition may be important factors contributing to the upper limit on maximal motor unit firing rate.

A mounting body of evidence suggests that Eye Movement Desensitization and Reprocessing therapy (EMDR) is successful in reducing the impact of posttraumatic symptoms. Although the exact mechanisms of action remain unknown, theories from the psychological to the neuroscientific continue to emerge, expand, and evolve. This study will examine four of the most prominent theories to date and weigh the evidence for and against each one. It will also review, compare, and contrast the theories, evaluate the research supporting each one, and propose the most likely explanation for EMDR’s success given the state of the research. Neurobiological mechanisms and correlates as well as the controversy over the use of eye movements will also be reviewed. Implications for future research will also be discussed.

The hyperventilation syndrome refers to a complex variety of symptoms which primarily influence the respiratory, cardiovascular, and musculoskeletal systems, and the syndrome is associated with a breathing pattern in excess of the body's demands. Psychologically, these symptoms mimic a panic attack and can cause severe anxiety in the person experiencing them. The present study was an attempt to determine whether respiratory feedback was a beneficial treatment when used to teach breathing retraining to improve the symptoms of hyperventilation in agoraphobic patients. A multiple baseline design across 4 subjects who had been diagnosed as suffering from an anxiety disorder, namely panic attacks, was used to test the experimental hypotheses. Dependent variables measured were respiration rate, respiration mode, heart rate, subjective anxiety, and symptom relief. The results indicated that all of the participants showed improvements on at least one of the physiological variables, but showed no change on one of the two psychological variables used in this study.

The Hyperventilation Syndrome (HVS) is characterized by episodic or sustained overbreathing (e.g., in excess of the body's needs). This can lead to a state of respiratory alkalosis causing both physiological and psychological disturbances, including cerebral and peripheral vasoconstriction, increased excitability of neurons, and anxiety. Clinically, HVS rarely is exhibited in the extreme form of tetany or syncopy. Participants in this study completed the State/Trait Anxiety Inventory (STAI) and the Nijmegen Questionnaire for Hyperventilation. Respiration was assessed in terms of rate and mode (e.g., diaphragmatic versus thoracic) while the participant sat at rest. There was found to be no significant correlation between the scores on the STAI and the Nijmegen Questionnaire. Respiration rate for the participants averaged higher than the normal rate for the non-clinical population at large. Age did not affect the degree of hyperventilation symptoms, but females were more likely than males to have hyperventilation symptoms.

No description available.

The drug ±3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a popular recreational substance among young people. Most prior research has not attempted to carefully emulate human ecstasy use patterns in animal investigations. The objectives of the present series of experiments were to develop a rat model of intermittent ecstasy use and to begin to characterize the acute and long-term physiological, behavioral, and neurochemical consequences of adolescent MDMA exposure. In Experiments I and II, male Sprague-Dawley rats received 20 mg/kg/day of MDMA on every fifth day from postnatal day 35 to 60. This regimen caused subtle reductions in cortical serotonin transporter (SERT) binding and dose dependently modified indices of attention, working memory, and anxiety-like behavior. Experiment III tested whether periadolescent MDMA exposure (10 mg/kg x 2) modified the responses to a MDMA binge (5 or 10 mg/kg x 4) in young adulthood. Adolescent MDMA completely blocked the hypoactivity and SERT reductions induced by adult MDMA treatments. Importantly, developmental MDMA exposure only partially reduced the hyperthermia evoked by the binge. The pharmacokinetic profile of early (PD 35) and late (PD 60) adolescent MDMA (10 mg/kg) treatments were compared in Experiment IV. Pharmacokinetic parameters (elimination half-life, peak concentration) did not differ by age for MDMA but PD 60 animals showed lower peak concentrations of the metabolite methylenedioxyamphetamine (MDA). Finally, the goal of Experiment V was to determine if MDMA induced decreases in SERT levels mediated the behavioral consequences. Rats received the binge (10 mg/kg x 4) in combination with pretreatment with the serotonin reuptake inhibitor citalopram (10 mg/kg). Citalopram blocked SERT reductions measured one week after dosing and prevented some of the MDMA induced alterations in complex behavior. These studies reveal that: (1) repeated exposure to a clinically relevant MDMA dose can reduce cognitive function and alter affective behavior, (2) adolescent MDMA can lead to MDMA tolerance in adulthood, (3) the behavioral toxicology of MDMA may not be exclusively mediated by decreases in SERT. Overall, these findings indicate that the enduring neurobiological consequences of MDMA may not be limited to the serotonergic system and have substantial public health implications for regular ecstasy users. Keywords. Adolescence, Behavior, Memory, Serotonin transporter, Temperature, Weight

Benzodiazepines (BZs) and selective serotonin reuptake inhibitors (SSRIs) have both been approved for use in the treatment of anxiety disorders. Benzodiazepines offer immediate therapeutic benefits; however, tolerance and the potential for abuse may limit their long-term use. While little or no abuse potential is associated with SSRI use, therapeutic benefit is achieved only after several weeks of chronic treatment. During initial SSRI treatment, symptoms of anxiety may increase in some individuals and can lead to incomplete remission of anxiety symptoms or non-compliance. Evidence for the short-term use of BZs with long-term SSRI treatment is limited but some reports suggest faster symptom remission and/or greater global anxiolytic effect compared to SSRI treatment alone. The goal of the present research was to investigate the extent to which combinations of BZs and SSRIs interact to reduce behavioral and physiological measures of anxiety-like behavior and to investigate the mechanisms underlying these interactions. Acute treatment with SSRIs was shown to increase anxiogenic-like measures of behavior, with differences in dose-dependent decreases in locomotor activity associated with fluoxetine and citalopram, while a non-selective BZ (diazepam) produced acute anxiolytic-like effects with dose-dependent decreases in locomotor activity. Combinations of SSRI+BZ produced acute anxiolytic-like effects, attenuating both the anxiogenic-like effects associated with SSRI treatment and decreased locomotor activity associated with BZs. Investigation with GABAA subunit selective ligands indicate that α2, 3, and/or 5 subunit containing GABAA receptors are likely involved in the anxiolytic-like effects and decreases in locomotor activity, while the role of a1 subunit containing GABAA receptor is unclear, but play no role in decreased locomotor activity or anxiolytic-like effect of combined treatment. Investigation with selective serotonin (5-HT) receptor subtype ligands indicates that 5-HT1A and 5-HT2C receptors are not involved in the anxiogenic-like effects of acute SSRI treatment in this model. Acute treatment with anxiolytic-like dose of BZ, and anxiogenic-like dose of SSRI and anxiolytic-like doses of combined SSRI+BZ all result in significant increases in stress hormone release following administration. Altogether, these results suggest that acute, combined SSRI+BZ treatment may be useful in decreasing measures of anxiety-like behavior and minimizing decreases in locomotor activity and are implicated in a complex relationship with the hypothalamic pituitary axis.