Faculty Bibliography

Using findings from the formative evaluation of the adaptation of the Collaborative HIV/AIDS Adolescent Mental Health Programme (CHAMP) family-based intervention in South Africa, known as the 'AmaQhawe Family Project', the potential role of 'micro-media' using a cartoon narrative for promoting health-enhancing behaviour change is explored. In particular, the cartoon narrative was found to be a useful medium for informing the development and diffusion of health-enhancing social representations that shape the potential for health-related behaviour change.

BACKGROUND: Risk-taking behavior is a major cause of morbidity and mortality in adolescence. In the context of decision theory and motivated (goal-directed) behavior, risk-taking reflects a pattern of decision-making that favors the selection of courses of action with uncertain and possibly harmful consequences. We present a triadic, neuroscience systems-based model of adolescent decision-making. METHOD: We review the functional role and neurodevelopmental findings of three key structures in the control of motivated behavior, i.e. amygdala, nucleus accumbens, and medial/ventral prefrontal cortex. We adopt a cognitive neuroscience approach to motivated behavior that uses a temporal fragmentation of a generic motivated action. Predictions about the relative contributions of the triadic nodes to the three stages of a motivated action during adolescence are proposed. RESULTS: The propensity during adolescence for reward/novelty seeking in the face of uncertainty or potential harm might be explained by a strong reward system (nucleus accumbens), a weak harm-avoidant system (amygdala), and/or an inefficient supervisory system (medial/ventral prefrontal cortex). Perturbations in these systems may contribute to the expression of psychopathology, illustrated here with depression and anxiety. CONCLUSIONS: A triadic model, integrated in a temporally organized map of motivated behavior, can provide a helpful framework that suggests specific hypotheses of neural bases of typical and atypical adolescent behavior.

BACKGROUND: Awareness of the impact and prevalence of autism spectrum disorders has significantly increased in recent years. Given the dearth of reliable interventions, there is great interest in demonstrating efficacy of the various treatment options. A growing body of evidence links autism spectrum disorders to abnormalities in serotonin function, and the selective serotonin reuptake inhibitors (SSRIs) have been utilized to target various symptoms of the disorders. This article reviews the available data on the efficacy and tolerability of SSRIs in individuals with autism spectrum disorders. Objectives for future research in this area will also be suggested. DATA SOURCES AND STUDY SELECTION: The entire PubMed database including MEDLINE (1966-July 2005) was searched for English-language biomedical articles. Search terms included autism, autism spectrum disorder, citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, pervasive developmental disorder, selective serotonin reuptake inhibitors, and sertraline. All clinical trials evaluating treatment outcomes associated with the use of SSRIs in managing symptoms of autism that were identified in the search were reviewed. All randomized controlled trials and open-label trials were included in this review. Case reports and case series were excluded. DATA SYNTHESIS: We identified 3 randomized controlled trials and 10 open-label trials or retrospective chart reviews on the use of SSRIs in autism and autism spectrum disorders. The SSRIs that have been studied in autism spectrum disorders are citalopram, escitalopram, fluoxetine, fluvoxamine, and sertraline. Most studies demonstrate significant improvement in global functioning and in symptoms associated with anxiety and repetitive behaviors. While side effects were generally considered to be mild, increased activation and agitation occurred in some subjects. CONCLUSIONS: Although SSRIs may demonstrate therapeutic benefit in autism spectrum disorders, methodological weaknesses of many of the clinical trials suggest the need for additional randomized controlled trials. Furthermore, given the increased awareness of the dangers associated with SSRI-induced activation and agitation, the presence of these side effects in the autistic population warrants closer attention to dosage, titration, and subject selection issues

Detection and discrimination of odors generally, if not always, occurs against an odorous background. On any given inhalation, olfactory receptor neurons will be activated by features of both the target odorant and features of background stimuli. To identify a target odorant against a background therefore, the olfactory system must be capable of grouping a subset of features into an odor object distinct from the background. Our previous work has suggested that rapid homosynaptic depression of afferents to the anterior piriform cortex (aPCX) contributes to both cortical odor adaptation to prolonged stimulation and habituation of simple odor-evoked behaviors. We hypothesize here that this process may also contribute to figure-ground separation of a target odorant from background stimulation. Single-unit recordings were made from both mitral/tufted cells and aPCX neurons in urethan-anesthetized rats and mice. Single-unit responses to odorant stimuli and their binary mixtures were determined. One of the odorants was randomly selected as the background and presented for 50 s. Forty seconds after the onset of the background stimulus, the second target odorant was presented, producing a binary mixture. The results suggest that mitral/tufted cells continue to respond to the background odorant and, when the target odorant is presented, had response magnitudes similar to that evoked by the binary mixture. In contrast, aPCX neurons filter out the background stimulus while maintaining responses to the target stimulus. Thus the aPCX acts as a filter driven most strongly by changing stimuli, providing a potential mechanism for olfactory figure-ground separation and selective reading of olfactory bulb output

Studied the effectiveness of a school-based mental health service model, PALS (Positive Attitudes toward Learning in School), focused on increasing initial and ongoing access to services, and promoting improved classroom and home behavior for children referred for Disruptive Behavior Disorder (DBD) from three high poverty urban elementary schools. Classrooms were randomly assigned to PALS or referral to a neighborhood mental health clinic, with children identified by teacher referral and follow-up parent andeher ratings. Results indicated significant service engagement and retention for PALS (n=60) versus families referred to clinic (n=30), with over 80% of PALS families retained in services for 12 months. PALS services were correlated with positive changes in children's behavior as rated by parents, and with improvements in children's academic performance as rated by teachers. Implications for the design and delivery of mental health services for children and families living in high-poverty urban communities are discussed.

Memory consolidation refers to a process by which newly learned information is made resistant to disruption. Traditionally, consolidation has been viewed as an event that occurs once in the life of a memory. However, considerable evidence now indicates that consolidated memories, when reactivated through retrieval, become labile (susceptible to disruption) again and undergo reconsolidation. Because memories are often interrelated in complex associative networks rather than stored in isolation, a key question is whether reactivation of one memory makes associated memories labile in a way that requires reconsolidation. We tested this in rats by creating interlinked associative memories using a second-order fear-conditioning task. We found that directly reactivated memories become labile, but indirectly reactivated (i.e., associated) memories do not. This suggests that memory reactivation produces content-limited rather than wholesale changes in a memory and its associations and explains why each time a memory is retrieved and updated, the entire associative structure of the memory is not grossly altered

The Continuous Delay Aversion Test (ConDAT), a new computer task for online monitoring and continuously measuring delay aversion (DA), is introduced. DA is a motivational style related to a shortened delay gradient which is proposed as a major endophenotype of attention deficit hyperactivity disorder (ADHD). It is characterised by avoiding or escaping from delay-rich situations despite the prospects of a reward. In each ConDAT trial the rapidly diminishing reward/delay ratio, which tends asymptotically towards zero, is visually presented on the computer screen. The test subject is permanently confronted with the question whether to quit or to continue the trial in the face of the deteriorating reward/time ratio. An elaborated control of stimuli and responses, including the sending of trigger codes to external recording devices, makes the task useful for neurophysiological or brain imaging experiments. Compared to existing tasks, the ConDAT is more flexible and sensitive due to its asymptotic open-ended trials and the interval-scaled output measure. Pilot data give evidence for satisfactory reliability and external validity of the task

Children and adolescents with attention-deficit/hyperactivity disorder (ADHD) have smaller cerebellar volumes, particularly in the posterior-inferior cerebellar vermis (lobules VIII-X). Functional activation of the human cerebellar vermis following stimulant administration has also been repeatedly demonstrated. There is no well-characterized dopaminergic pathway that projects to the posterior-inferior cerebellar vermis, although the dopamine transporter (DAT) and tyrosine hydroxylase (TH) have been localized in the posterior-inferior vermis in the non-human primate by immunohistochemistry. We hypothesized that DA neurotransmission may occur in localized 'hot spots' in the cerebellar vermis, and if so, that differences in such neurotransmission might be relevant to the pathophysiology of ADHD. To investigate this hypothesis, cerebellar tissue was obtained from rats and non-human primates. Catecholamines were extracted and analyzed using HPLC with coulometric detection. A regional gradient of norepinephrine (NE) and DA was found throughout the cerebellum with NE levels always roughly 10-40-fold higher than DA in both rats and monkeys. In addition, in vivo microdialysis studies were performed in the rat posterior-inferior cerebellar vermis in anesthetized animals. Significant NE overflow was observed over baseline following reverse microdialysis induced release by potassium or d-amphetamine. DA overflow was not observed over baseline for potassium stimulation, but was significant for d-amphetamine stimulation. These studies refute the hypothesis that DA neurotransmission normally occurs in the rat cerebellar vermis, but highlight that vermal DA is released by d-amphetamine. The presence of DAT may therefore allow for enhanced regulation of NE and not regulation of released DA

BACKGROUND: Current theories suggest a role for frontal-striatal circuits in the pathogenesis of attention-deficit/hyperactivity disorder (ADHD). METHODS: We used magnetoencephalography (MEG) to measure event-related brain activity during a simplified version of the Wisconsin Card Sorting Test in children with DSM-IV combined type ADHD (ADHD-C) or predominantly inattentive type ADHD (ADHD-PI) and in age- and intelligence-matched control children. RESULTS: In control children, set-shifting cues evoked a higher degree of activation in the medial temporal lobe (MTL) between 200 and 300 msec than non-shifting cues, with MTL activation predicting later activity in left anterior cingulate cortex (ACC) (at 400-500 msec). This MTL-ACC response pattern was diminished in children with ADHD. By contrast, children with ADHD showed early activity in regions barely activated in control children, such as left inferior parietal lobe and posterior superior temporal gyrus. CONCLUSIONS: These preliminary data support theories of frontal dysfunction in ADHD but also suggest that deficits in higher-level functions might be secondary to disruptions in earlier limbic processes