Faculty Bibliography

To better characterize fluent and nonfluent variants of primary progressive aphasia (PPA). Although investigators have recognized both fluent and nonfluent patients with PPA, the clinical and neuroimaging features of these variants have not been fully defined. We present clinical and neuropsychological data on 47 PPA patients comparing the fluent (n=21) and nonfluent (n=26) subjects. We further compared language features with PET/SPECT data available on 39 of these patients. Compared to the nonfluent PPA patients, those with fluent PPA had greater impairment of confrontational naming and loss of single word comprehension. They also exhibited semantic paraphasic errors and loss of single word comprehension. Patients with nonfluent PPA were more likely to be female, were more often dysarthric, and exhibited phonological speech errors in the absence of semantic errors. No significant differences were seen with regard to left hemisphere abnormalities, suggesting that both variants result from mechanisms that overlap frontal, temporal, and parietal regions. Of the language measures, only semantic paraphasias were strongly localized, in this case to the left temporal lobe. Fluent and nonfluent forms of PPA are clinically distinguishable by letter fluency, single word comprehension, object naming, and types of paraphasic errors. Nevertheless, there is a large amount of overlap between dysfunctional anatomic regions associated with these syndromes

INTRODUCTION: The mandibular rami and their endochondrally growing condyles develop in many directions relative to the variable anatomic patterns of the nasomaxilla and middle cranial fossae during growth and response to orthopedic treatment. METHODS: High-resolution magnetic resonance images were used to compare 3-dimensional (3D) growth vectors of skeletal displacement and bone remodeling in 25 untreated subjects with Class II malocclusions, 28 subjects with Class II malocclusions who were treated with Frankel appliance therapy, and 25 subjects with normal occlusions. Marked differences were noted over an 18-month observation period. The 3D coordinates of anatomic landmarks were registered by Procrustes fit to control for rotation, translation, and scale differences. RESULTS: Compared with untreated Class II and normal-occlusion subjects, the treated group showed highly significant differences in the 3D displacement/remodeling vectors of gonion and pterygomaxillary fissure relative to condylion and middle cranial fossae bilateral skeletal landmarks, by using both permutation tests ( P < .001) and a general linear multivariate model ( P < .0001). CONCLUSIONS: In a prospective and systematically controlled study, we quantitatively described significant 3D rami skeletal compensations in the structural assembly of facial morphogenesis at the beginning of the adolescent growth spurt using novel modeling techniques. These techniques have facilitated quantification of relative 3D growth vectors to illustrate skeletal changes with Frankel appliance therapy. Future studies are required to assess the long-term clinical significance of our findings.

INTRODUCTION: Three-dimensional (3D) craniofacial images are commonly used in clinical studies in orthodontics to study developmental and morphologic relationships. METHODS: We used 3D magnetic resonance imaging to study relationships among craniofacial components during the pubertal growth spurt and in response to Frankel appliance therapy. The sample for this prospective study was 156 high-resolution magnetic resonance images with 1 mm isotropic voxel resolution of 78 subjects taken initially (T1) and 18 +/- 1 months (T2) after treatment or an observation period. The subjects were Brazilian children; 28 were treated and 25 were untreated for Class II malocclusion, and 25 were untreated with normal occlusions. A Procrustes geometric transformation of 3D skeletal landmarks was used to assess growth or treatment alterations from T1 to T2. The landmarks were located on the mandibular rami and the other craniofacial parts specifically related to the mandibular growth (the middle cranial fossae and the posterior part of the bilateral nasomaxilla). This allowed visualization of the entire volumetric dataset with an interactive 3D display. RESULTS: Statistically significant differences were found in the relative 3D skeletal growth directions from T1 to T2 for treated vs untreated Class II children (Bonferroni-adjusted P < .001) and for treated Class II vs normal-occlusion subjects ( P < .001). The major differences in the treated group were increased mandibular rami vertical dimensions and more forward rami relative to the posterior nasomaxilla and the middle cranial fossae. Principal component analysis made it possible to show individual variability and group differences in the principal dimensions of skeletal change. CONCLUSIONS: These methods are generalizable to other imaging techniques and 3D samples, and significantly enhance the potential of systematically controlled data collection and analysis of bony structures in 3 dimensions for quantitative assessment of patient parameters in craniofacial biology.

A systematic review was undertaken of scientifically rigorous studies of family-based services in children's health and mental health. From a pool of over 4000 articles since 1980 in health and mental health that examined either specific family-based interventions for families of children or the processes of involvement, 41 studies were identified that met the methodological criteria for inclusion. These 41 studies encompassed 3 distinct categories: families as recipients of interventions (e.g., family education, support, engagement, empowerment); (b) families as co-therapists; and (c) studies of the processes of involvement (e.g., therapeutic alliance, engagement, empowerment, expectancies, and choice). Too few experimental studies exist to conclude decisively that family-based services improve youth clinical outcomes. However, those studies that have been rigorously examined demonstrate unequivocal improvements in other types of outcomes, such as retention in services, knowledge about mental health issues, self-efficacy, and improved family interactions - all outcomes that are essential ingredients of quality care. Four implications are drawn from this review. (1) Effective family education and support interventions from studies of adults with mental illnesses and from studies of families of high-risk infants exist and can be imported into the field of children's mental health. (2) The range of outcomes that are typically assessed in clinical treatment studies is too narrow to afford an adequate view of the impact of family-based interventions. A broader view of outcomes is needed. (3) The absence of a robust literature on process variables other than therapeutic alliance limits conclusions about how and why interventions are effective. Attention to the processes by which families become involved in services will require a more robust and nuanced range of studies that attend simultaneously to processes of change and to outcome improvement. (4) Linkage of effective family-based interventions to delivery of evidence-based services is likely to amplify the impact of those services and improve outcomes for youth and families.

OBJECTIVE:: Panic disorder (PD) has been linked to perturbed processing of threats. This study tested the hypotheses that offspring of parents with PD and offspring with anxiety disorders display relatively greater sensitivity and attention allocation to fear provocation. METHOD:: Offspring of adults with PD, major depressive disorder (MDD), or no disorder (ages 9-19) viewed computer-presented face photographs depicting angry, fearful, and happy faces. Offspring rated (1) subjectively experienced fear level, (2) how hostile the face appeared, and (3) nose width. Attention allocation was indexed by latency to perform ratings. RESULTS:: Compared with offspring of parents without PD (n = 79), offspring of PD parents (n = 65) reported significantly more fear and had slower reaction times to rate fear, controlling for ongoing anxiety disorder in the offspring. Offspring with an anxiety disorder (n = 65) reported significantly more fear than offspring without an anxiety disorder but not when parental PD was controlled. Social phobia but no other anxiety disorder in offspring was associated with slower reaction times for fear ratings (but not greater fear ratings). Parental PD and offspring social phobia independently predicted slower reaction time. CONCLUSIONS:: Results support an association between parental PD and offspring responses to fear provocation. Social phobia in children may have a specific relationship to allocation of attention to subjective anxiety during face viewing

Nitric oxide (NO) has been widely implicated in synaptic plasticity and memory formation. In studies of long-term potentiation (LTP), NO is thought to serve as a 'retrograde messenger' that contributes to presynaptic aspects of LTP expression. In this study, we examined the role of NO signaling in Pavlovian fear conditioning. We first show that neuronal nitric oxide synthase is localized in the lateral nucleus of the amygdala (LA), a critical site of plasticity in fear conditioning. We next show that NO signaling is required for LTP at thalamic inputs to the LA and for the long-term consolidation of auditory fear conditioning. Collectively, the findings suggest that NO signaling is an important component of memory formation of auditory fear conditioning, possibly as a retrograde signal that participates in presynaptic aspects of plasticity in the LA

The authors examined the neuropsychological status of 22 preschoolers at risk for attention-deficit/hyperactivity disorder (ADHD) and 50 matched control children, using measures of nonverbal working memory, perceptual and motor inhibition, and memory for relative time. All tasks included paired control conditions, which allowed for the isolation of discrete executive function constructs. Group differences were evident on several measures of neuropsychological functioning; however, after accounting for nonexecutive abilities, no deficits could be attributed to specific functions targeted by the tasks. Performance on executive measures was not related to objective indices of activity level or ratings of ADHD symptoms. Yet, the fact that at-risk preschoolers were highly symptomatic casts doubt on whether executive function deficits and/or frontostriatal networks contribute etiologically to early behavioral manifestations of ADHD.

CONTEXT: While numerous magnetic resonance imaging (MRI) studies have evaluated adults with bipolar disorder (BPD), few have examined MRI changes in children with BPD. OBJECTIVE: To determine volume alterations in children with BPD using voxel-based morphometry, an automated MRI analysis method with reduced susceptibility to various biases. A priori regions of interest included amygdala, accumbens, hippocampus, dorsolateral prefrontal cortex (DLPFC), and orbitofrontal cortex. DESIGN: Ongoing study of the pathophysiology of pediatric BPD. SETTING: Intramural National Institute of Mental Health; approved by the institutional review board.Patients Pediatric subjects with BPD (n = 20) with at least 1 manic or hypomanic episode meeting strict DSM-IV criteria for duration and elevated, expansive mood. Controls (n = 20) and their first-degree relatives lacked psychiatric disorders. Groups were matched for age and sex and did not differ in IQ. MAIN OUTCOME MEASURES: With a 1.5-T MRI machine, we collected 1.2-mm axial sections (124 per subject) with an axial 3-dimensional spoiled gradient recalled echo in the steady state sequence. Image analysis was by optimized voxel-based morphometry. RESULTS: Subjects with BPD had reduced gray matter volume in the left DLPFC. With a less conservative statistical threshold, additional gray matter reductions were found in the left accumbens and left amygdala. No difference was found in the hippocampus or orbitofrontal cortex. CONCLUSIONS: Our results are consistent with data implicating the prefrontal cortex in emotion regulation, a process that is perturbed in BPD. Reductions in amygdala and accumbens volumes are consistent with neuropsychological data on pediatric BPD. Further study is required to determine the relationship between these findings in children and adults with BPD

In this event-related functional magnetic resonance imaging (fMRI) study, we provide evidence that the role of the anterior cingulate cortex (ACC) in cognitive control may not be unitary, as the responses of different ACC subregions vary depending upon the nature of task-irrelevant information. More specifically, using the color-word Stroop task (congruent, incongruent, and neutral trial types), we examined the degree to which increases in neural activity within ACC are specific to conditions of conflict, as posited by the conflict monitoring theory (Botvinick et al. [1999]: Rev Neurosci 10:49-57; Carter et al. [1998]: Science 280:747-749). Although incongruent and congruent trials both involve two competing sources of color information (color word and ink color), only incongruent trials involve a direct conflict between task-relevant and task-irrelevant information. Although the anterior division of the ACC rostral zone exhibited conflict specific increases in neural activity (i.e., incongruent > congruent = neutral), the posterior division exhibited a more generalized pattern, increasing whenever the task-irrelevant information was color related, regardless of whether it was conflicting (i.e., incongruent and congruent > neutral). Our data thus suggest a possible functional differentiation within the ACC. As such, it is unlikely that the role of the ACC in cognitive control will be able to be accommodated by a single unifying theory