Biomedical subjects

Charlotte A Boettiger

Publications and source records attributed to Charlotte A Boettiger.

4 recordsLinked to original sources

PubMed2006

Endogenous opioid blockade and impulsive responding in alcoholics and healthy controls.

The opioid receptor antagonist naltrexone (NTX) is one of few approved treatments for alcoholism, yet the mechanism by which it reduces drinking remains unclear. In rats, NTX reduces morphine-induced impulsive choice bias; however, nothing is known about the drug's effect on discrete aspects of impulsive behavior in humans, such as decision-making and inhibitory control. Here, we used a modified delay discounting procedure to investigate whether NTX improves decision-making or inhibitory control in humans. We measured the effect of acute NTX (50 mg) on choice between smaller sooner (SS) and larger later monetary rewards and on response errors (motor mismatch) in a high conflict condition in a group of abstinent alcoholics (AA) and healthy control subjects (CS). We previously reported that AA selected the SS option significantly more often than did CS in this paradigm. If the choice bias of AA is due to enhanced endogenous opioid signaling in response to potential reward, NTX should reduce such bias in the AA group. We found that NTX did not reliably reduce impulsive choice in the AA group; however, NTX's effect on choice bias across individuals was robustly predictable. NTX's effect on choice bias was significantly correlated with scores on Rotter's Locus of Control (LOC) scale; increasingly internal LOC scores predicted increasing likelihood of impulsive choices on NTX. In addition, we found that NTX significantly enhanced control of motor responses, particularly within the CS group. These results suggest that endogenous opioids may impair response selection during decision-making under conflict, and that NTX's effects on explicit decision-making are personality-dependent. Determining the biological basis of this dependence could have important implications for effective alcoholism treatment.

Adult↗

PubMed2005

Frontal networks for learning and executing arbitrary stimulus-response associations.

Flexible rule learning, a behavior with obvious adaptive value, is known to depend on an intact prefrontal cortex (PFC). One simple, yet powerful, form of such learning consists of forming arbitrary stimulus-response (S-R) associations. A variety of evidence from monkey and human studies suggests that the PFC plays an important role in both forming new S-R associations and in using learned rules to select the contextually appropriate response to a particular stimulus cue. Although monkey lesion studies more strongly implicate the ventrolateral PFC (vlPFC) in S-R learning, clinical data and neurophysiology studies have implicated both the vlPFC and the dorsolateral region (dlPFC) in associative rule learning. Previous human imaging studies of S-R learning tasks, however, have not demonstrated involvement of the dlPFC. This may be because of the design of previous imaging studies, which used few stimuli and used explicitly stated one-to-one S-R mapping rules that were usually practiced before scanning. Humans learn these rules very quickly, limiting the ability of imaging techniques to capture activity related to rule acquisition. To address these issues, we performed functional magnetic resonance imaging while subjects learned by trial and error to associate sets of abstract visual stimuli with arbitrary manual responses. Successful learning of this task required discernment of a categorical type of S-R rule in a block design expected to yield sustained rule representation. Our results show that distinct components of the dorsolateral, ventrolateral, and anterior PFC, lateral premotor cortex, supplementary motor area, and the striatum are involved in learning versus executing categorical S-R rules.

Adult↗

PubMed2005

Impulsive responding in alcoholics.

BACKGROUND: Impaired decision-making is one diagnostic characteristic of alcoholism. Quantifying decision-making with rapid and robust laboratory-based measures is thus desirable for the testing of novel treatments for alcoholism. Previous research has demonstrated the utility of delay discounting (DD) tasks for quantifying differences in decision-making in substance abusers and normal controls. In DD paradigms subjects choose between a small, immediate reward and a larger, delayed reward. METHODS: We used a novel computerized DD task to demonstrate that abstinent alcoholics (AA, n=14) choose the larger, delayed option significantly less often than control subjects (n=14; p<0.02). This difference in choice tendency was independent of subject age, gender, years of education, or socio-economic status. RESULTS: All subjects discounted as a function of reward delay and amount, with alcoholics demonstrating steeper discounting curves for both variables. This tendency to discount delayed rewards was positively correlated with subjective reports of both alcohol addiction severity (Drug Use Screening Inventory-Revised, Domain 1, p<0.01), and impulsivity (Barratt Impulsivity Scale-11, p<0.004). Novel aspects of this new paradigm include an element of time pressure, an additional experimental condition that evaluated motor impulsivity by assessing the ability to inhibit a pre-potent response, and another control condition to requiring non-subjective choice. CONCLUSIONS: Non-alcoholic controls and alcoholics did not differ on motor impulsivity or non-subjective choice, suggesting that the differing choice behavior of the two groups was due mainly to differences in cognitive impulsivity.

Adult↗

PubMed2004

Cellular, circuit, and synaptic mechanisms in song learning.

Songbirds, much like humans, learn their vocal behavior, and must be able to hear both themselves and others to do so. Studies of the brain areas involved in singing and song learning could reveal the underlying neural mechanisms. Here we describe experiments that explore the properties of the songbird anterior forebrain pathway (AFP), a basal ganglia-forebrain circuit known to be critical for song learning and for adult modification of vocal output. First, neural recordings in anesthetized, juvenile birds show that auditory AFP neurons become selectively responsive to the song stimuli that are compared during sensorimotor learning. Individual AFP neurons develop tuning to the bird's own song (BOS), and in many cases to the tutor song as well, even when these stimuli are manipulated to be very different from each other. Such dual selectivity could be useful in the BOS-tutor song comparison critical to song learning. Second, simultaneous neural recordings from the AFP and its target nucleus in the song motor pathway in anesthetized adult birds reveal correlated activity that is preserved through multiple steps of the circuits for song, including the AFP. This suggests that the AFP contains highly functionally interconnected neurons, an architecture that can preserve information about the timing of firing of groups of neurons. Finally, in vitro studies show that recurrent synapses between neurons in the AFP outflow nucleus, which are expected to contribute importantly to AFP correlation, can undergo activity-dependent and timing-sensitive strengthening. This synaptic enhancement appears to be restricted to birds in the sensory critical and early sensorimotor phases of learning. Together, these studies show that the AFP contains cells that reflect learning of both BOS and tutor song, as well as developmentally regulated synaptic and circuit mechanisms well-suited to create temporally organized assemblies of such cells. Such experience-dependent sensorimotor assemblies are likely to be critical to the AFP's role in song learning. Moreover, studies of such mechanisms in this basal ganglia circuit specialized for song may shed light more generally on how basal ganglia circuits function in guiding motor learning using sensory feedback signals.

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