Faculty Bibliography

BACKGROUND: An increasing number of youth are being diagnosed with, and treated for, bipolar disorder (BD). Controversy exists about whether youth with non-episodic irritability and symptoms of attention deficit hyperactivity disorder (ADHD) should be considered to have a developmental presentation of mania. METHOD: A selective review of the literature related to this question, along with recommendations to guide clinical assessment. RESULTS: Data indicate differences between youth with episodic mania and those with non-episodic irritability in longitudinal diagnostic associations, family history, and pathophysiology. In youth with episodic mania, elation and irritability are both common during manic episodes. CONCLUSIONS: In diagnosing mania in youth, clinicians should focus on the presence of episodes that consist of a distinct change in mood accompanied by concurrent changes in cognition and behavior. BD should not be diagnosed in the absence of such episodes. In youth with ADHD, symptoms such as distractibility and agitation should be counted as manic symptoms only if they are markedly increased over the youth's baseline symptoms at the same time that there is a distinct change in mood and the occurrence of other associated symptoms of mania. Although different techniques for diagnosing comorbid illnesses have not been compared systematically, it appears most rational to diagnose co-occurring illnesses such as ADHD only if the symptoms of the co-occurring illness are present when the youth is euthymic.

Human cerebral development is remarkably protracted. Although microstructural processes of neuronal maturation remain accessible only to morphometric post-mortem studies, neuroimaging tools permit the examination of macrostructural aspects of brain development. The analysis of resting-state functional connectivity (FC) offers novel possibilities for the investigation of cerebral development. Using seed-based FC methods, we examined the development of 5 functionally distinct cingulate-based intrinsic connectivity networks (ICNs) in children (n = 14, 10.6 +/- 1.5 years), adolescents (n = 12, 15.4 +/- 1.2) and young adults (n=14, 22.4 +/- 1.2). Children demonstrated a more diffuse pattern of correlation with voxels proximal to the seed region of interest (ROI) ('local FC'), whereas adults exhibited more focal patterns of FC, as well as a greater number of significantly correlated voxels at long distances from the seed ROI. Adolescents exhibited intermediate patterns of FC. Consistent with evidence for different maturational time courses, ICNs associated with social and emotional functions exhibited the greatest developmental effects. Our findings demonstrate the utility of FC for the study of developing functional organization. Moreover, given that ICNs are thought to have an anatomical basis in neuronal connectivity, measures of FC may provide a quantitative index of brain maturation in healthy subjects and those with neurodevelopmental disorders

The role of interpositus nuclei (IN) in timing in the sub-second range is well supported in eyeblink conditioning studies. Timing impairments shown in the seconds range in patients with intermediate cerebellar lesion, and known intermediate cerebellar cortex projection to IN raise the question of a possible involvement of IN in timing in the supra-second range as well. To address this question, we tested rats (Sprague-Dawley) given bilateral lesions of IN with Colchicine in a 2- vs. 8-s temporal discrimination task, followed by three daily sessions of a temporal bisection tests with five added intermediate non-reinforced durations. IN lesioned rats showed normal acquisition of the temporal discrimination, but a transient impairment of temporal sensitivity during the bisection tests. In addition, their response latencies suggested a different behavioral strategy from that of control animals. Our results indicate that the IN of the cerebellum may not be critically involved in temporal processing in the 2-8 s range, but may play a role in the cognitive processes that access temporal information in the mediation of choice behavior.

Fetal alcohol syndrome (FAS), a condition occurring in some children of mothers who have consumed alcohol during pregnancy, is characterized by physical deformities and learning and memory deficits. The chick hippocampus, whose functions are controlled by interneurons expressing calcium-binding proteins parvalbumin (PV) and calretinin (CR), is involved in learning and memory mechanisms. Effects on growth and development and hippocampal morphology were studied in chick embryos exposed to 5% and 10% ethanol volume/volume (vol/vol) for 2 or 8 days of gestation. There was a significant dose-dependent reduction (P<.05) in body weight and mean number per section of PV and CR expressing hippocampal neurons in ethanol-exposed chicks, without alterations in neuronal nuclear size or hippocampal volume, compared appropriate controls. Moreover, when chicks exposed to 5% ethanol for 2 and 8 days of gestation were compared, no significant differences were found in body parameters or neuronal counts. Similarly, exposure to 10% ethanol did not induce any significant changes in chicks exposed for 2 or 8 gestational days. Thus, these results suggest that gestational ethanol exposure induces a reduction in the mean number per section of PV and CR expressing hippocampal neurons, and could be a possible mechanism responsible for learning and memory disorders in FAS.

BACKGROUND: Discordance of birth weight has been observed in twin pairs, though little is known about prenatal and early neonatal discordance of head and brain size, and the role that zygosity and chorionicity play in discordances of early brain development in twins. AIMS: To compare prenatal and neonatal discordances of head size in monozygotic-monochorionic (MZ-MC), monozygotic-dichorionic (MZ-DC), and same-sex dizygotic-dichorionic twin pairs (DZ). STUDY DESIGN: Subjects prospectively had ultrasounds at 22 and 32 weeks gestational age, and magnetic resonance imaging (MRI) of the brain MRI after birth. SUBJECTS: 88 twin pairs recruited from two university hospital prenatal diagnostic clinics; 22 MZ-MC, 17 MZ-DC, and 49 same-sex DZ pairs. OUTCOME MEASURES: Discordance of head circumference (HC) and weight at 22 weeks, 32 weeks and birth, as well as intracranial volume (ICV) on neonatal MRI. RESULTS: There were no group differences in discordance of head circumference and weight on the 22 or 32 week ultrasounds, or at birth. MZ-MC twins tended to have numerically greater discordances of HC and weight. There was a significant group difference in ICV on neonatal MRI (ANOVA, p=0.0143), with DZ twins having significantly greater discordance than MZ-MC (p=0.028) or MZ-DC (p=0.0131) twins. CONCLUSIONS: This study indicates that zygosity and chorionicity do not contribute to significant discordances of head size in late prenatal development. DZ twins do have significantly greater discordances of ICV on neonatal MRI, suggesting a relatively greater genetic influence on brain growth in the first weeks after birth.

Mood, attention and motivation co-vary with activity in the neuromodulatory systems of the brain to influence behaviour. These psychological states, mediated by neuromodulators, have a profound influence on the cognitive processes of attention, perception and, particularly, our ability to retrieve memories from the past and make new ones. Moreover, many psychiatric and neurodegenerative disorders are related to dysfunction of these neuromodulatory systems. Neurons of the brainstem nucleus locus coeruleus are the sole source of noradrenaline, a neuromodulator that has a key role in all of these forebrain activities. Elucidating the factors that control the activity of these neurons and the effect of noradrenaline in target regions is key to understanding how the brain allocates attention and apprehends the environment to select, store and retrieve information for generating adaptive behaviour

This article summarizes current research related to autism spectrum disorders. Current epidemiological trends, theories about aetiology, and relevant issues in assessment and diagnosis of autism spectrum disorders are discussed

The mechanisms underlying off-line consolidation of memory during sleep are elusive. Learning of hippocampus-dependent tasks increases neocortical slow oscillation synchrony, and thalamocortical spindle and hippocampal ripple activity during subsequent non-rapid eye movement sleep. Slow oscillations representing an oscillation between global neocortical states of increased (up-state) and decreased (down-state) neuronal firing temporally group thalamic spindle and hippocampal ripple activity, which both occur preferentially during slow oscillation up-states. Here we examined whether slow oscillations also group learning-induced increases in spindle and ripple activity, thereby providing time-frames of facilitated hippocampus-to-neocortical information transfer underlying the conversion of temporary into long-term memories. Learning (word-pairs in humans, odor-reward associations in rats) increased slow oscillation up-states and, in humans, shaped the timing of down-states. Slow oscillations grouped spindle and rat ripple activity into up-states under basal conditions. Prior learning produced in humans an increase in spindle activity focused on slow oscillation up-states. In rats, learning induced a distinct increase in spindle and ripple activity that was not synchronized to up-states. Event-correlation histograms indicated an increase in spindle activity with the occurrence of ripples. This increase was prolonged after learning, suggesting a direct temporal tuning between ripples and spindles. The lack of a grouping effect of slow oscillations on learning-induced spindles and ripples in rats, together with the less pronounced effects of learning on slow oscillations, presumably reflects a weaker dependence of odor learning on thalamo-neocortical circuitry. Slow oscillations might provide an effective temporal frame for hippocampus-to-neocortical information transfer only when thalamo-neocortical systems are already critically involved during learning