Faculty Bibliography

The BOLD signal measured in fMRI studies depends not only on neuronal activity, but also on other parameters like tissue vascularization, which may vary between subjects and between brain regions. A correction for variance from vascularization effects can thus lead to improved group statistics by reducing inter-subject variability. The fractional amplitude of low-frequency fluctuations (fALFF) as determined in a resting-state scan has been shown to be dependent on vascularization. Here we present a correction method termed RESCALE (REsting-state based SCALing of parameter Estimates) that uses local information to compute a voxel-wise scaling factor based on the correlation structure of fALFF and task activation parameter estimates from within a cube of 3 x 3 x 3 surrounding that voxel. The scaling method was used on a visuo-motor paradigm and resulted in a consistent increase in t-values in all task-activated cortical regions, with increases in peak t-values of 37.0% in the visual cortex and 12.7% in the left motor cortex. The RESCALE method as proposed herein can be easily applied to all task-based fMRI group studies provided that resting-state data for the same subject group is also acquired.

Analyses of intrinsic fMRI BOLD signal fluctuations reliably reveal correlated and anticorrelated functional networks in the brain. Because the BOLD signal is an indirect measure of neuronal activity and anticorrelations can be introduced by preprocessing steps, such as global signal regression, the neurophysiological significance of correlated and anticorrelated BOLD fluctuations is a source of debate. Here, we address this question by examining the correspondence between the spatial organization of correlated BOLD fluctuations and correlated fluctuations in electrophysiological high gamma power signals recorded directly from the cortical surface of 5 patients. We demonstrate that both positive and negative BOLD correlations have neurophysiological correlates reflected in fluctuations of spontaneous neuronal activity. Although applying global signal regression to BOLD signals results in some BOLD anticorrelations that are not apparent in the ECoG data, it enhances the neuronal-hemodynamic correspondence overall. Together, these findings provide support for the neurophysiological fidelity of BOLD correlations and anticorrelations.

This study examined the relationship between therapist factors and child outcomes in anxious youth who received cognitive-behavioral therapy (CBT) as part of the Child-Adolescent Anxiety Multimodal Study (CAMS). Of the 488 youth who participated in the CAMS project, 279 were randomly assigned to one of the CBT conditions (CBT only or CBT plus sertraline). Participants included youth (ages 7-17; M = 10.76) who met criteria for a principal anxiety disorder. Therapists included 38 cognitive-behavioral therapists. Therapist style, treatment integrity, and therapist experience were examined in relation to child outcome. Child outcome was measured via child, parent, and independent evaluator report. Therapists who were more collaborative and empathic, followed the treatment manual, and implemented it in a developmentally appropriate way had youth with better treatment outcomes. Therapist "coach" style was a significant predictor of child-reported outcome, with the collaborative "coach" style predicting fewer child-reported symptoms. Higher levels of therapist prior clinical experience and lower levels of prior anxiety-specific experience were significant predictors of better treatment outcome. Findings suggest that although all therapists used the same manual-guided treatment, therapist style, experience, and clinical skills were related to differences in child outcome. Clinical implications and recommendations for future research are discussed.

BACKGROUND: Obesity is associated with poor asthma outcomes; weight loss improves such outcomes. Inaccurate recognition of obesity may impede weight control. PURPOSE: We examined perception of weight by early adolescents with uncontrolled asthma and their caregivers, and tested the relationship between medical visit frequency and accuracy of perceived weight status. METHODS: A total of 373 adolescents and their caregivers reported the adolescent's height/weight and weight perception; caregivers reported healthcare utilization. We measured height/weight. Logistic regression modeled accuracy of weight perception. RESULTS: A total of 43.7 % of the overweight/obese adolescents and caregivers accurately perceived weight status. BMI percentile [odds ratio (OR) = 1.19, confidence interval (CI) = 1.10-1.28] and total medical visits (OR = 1.18, CI = 1.05-1.33) were associated with higher accuracy in caregivers. Total medical visits (OR = 0.84, CI = 0.74-0.96) was associated with lower accuracy in adolescents. CONCLUSIONS: Accurate perception of weight status was poor for overweight adolescents with uncontrolled asthma and their caregivers. Frequent medical visits were associated with improved caregivers' but not adolescents' perceptions.

PURPOSE: Remelted highly crosslinked polyethylenes (HXLPEs) were introduced in total knee replacement (TKR) starting in 2001 to reduce wear and particle-induced lysis. The purpose of this study was to investigate the damage mechanisms and oxidative stability of remelted HXLPEs used in TKR. METHODS: A total of 186 posteriorly stabilised tibial components were retrieved at consecutive revision operations. Sixty nine components were identified as remelted HXLPE. The conventional inserts were implanted for 3.4 +/- 2.7 years, while the remelted components were implanted 1.4 +/- 1.2 years. Oxidation was assessed using Fourier transform infrared spectroscopy. RESULTS: Remelted HXLPE inserts exhibited lower oxidation indices compared to conventional inserts. We were able to detect slight regional differences within the HXLPE cohort, specifically at the bearing surface. CONCLUSION: Remelted HXLPE was effective at reducing oxidation in comparison to gamma inert sterilised controls. Additional long-term HXLPE retrievals are necessary to ascertain the long term in vivo stability of these materials in TKR.

It is notoriously difficult to name odours. Without the benefit of non-olfactory information, even common household smells elude our ability to name them. The neuroscientific basis for this olfactory language 'deficit' is poorly understood, and even basic models to explain how odour inputs gain access to transmodal representations required for naming have not been put forward. This study used patients with primary progressive aphasia, a clinical dementia syndrome characterized by primary deficits in language, to investigate the interactions between olfactory inputs and lexical access by assessing behavioural performance of olfactory knowledge and its relationship to brain atrophy. We specifically hypothesized that the temporal pole would play a key role in linking odour object representations to transmodal networks, given its anatomical proximity to olfactory and visual object processing areas. Behaviourally, patients with primary progressive aphasia with non-semantic subtypes were severely impaired on an odour naming task, in comparison with an age-matched control group. However, with the availability of picture cues or word cues, odour matching performance approached control levels, demonstrating an inability to retrieve but not to recognize the name and nature of the odorant. The magnitude of cortical thinning in the temporal pole was found to correlate with reductions in odour familiarity and odour matching to visual cues, whereas the inferior frontal gyrus correlated with both odour naming and matching. Volumetric changes in the mediodorsal thalamus correlated with the proportion of categorical mismatch errors, indicating a possible role of this region in error-signal monitoring to optimize recognition of associations linked to the odour. A complementary analysis of patients with the semantic subtype of primary progressive aphasia, which is associated with marked temporopolar atrophy, revealed much more pronounced impairments of odour naming and matching. In identifying the critical role of the temporal pole and inferior frontal gyrus in transmodal linking and verbalization of olfactory objects, our findings provide a new neurobiological foundation for understanding why even common odours are hard to name.

This study examined the comorbidity of anxiety disorders and its predictors in a large, clinically referred sample of children and adolescents. Participants were 608 youth aged 4-18 years presenting at a large anxiety clinic for assessment and treatment of anxiety or mood related problems. The diagnoses were determined using the Anxiety Disorder Interview Schedule, Child/Parent versions. Sixty three percent of the participants had an additional diagnosis of an anxiety or depressive disorder. Comorbidity patterns differed based on the principal diagnostic category. Older children and females with anxiety were more likely to have a comorbid anxiety disorder. The presence of a medical condition increased the odds of having a comorbid anxiety disorder as well. This is the largest clinical sample of children and adolescents in which comorbidity of emotional disorders has been examined. Understanding the common patterns of comorbidity has important implications for future classification and treatment planning of childhood anxiety disorders.

Abstract The relationship between specific genes and particular diseases in neuropsychiatry is unclear, and newer studies focus on shared domains of neurobiological and cognitive pathology across different disorders. This paper reviews the evidence for an association between schizophrenia and frontotemporal dementia, including symptom similarity, familial co-morbidity, and neuroanatomical changes. Genetic as well as epigenetic findings from both schizophrenia and frontotemporal dementia are also discussed. As a result, we introduce the hypothesis of a shared susceptibility for certain subgroups of schizophrenia and frontotemporal dementia. This common causation may involve the same gene(s) at different stages of life: early in schizophrenia and late in frontotemporal dementia. Additionally, we provide a rationale for future research that should emphasize both genetic and cognitive parallels between certain forms of schizophrenia and frontotemporal dementia in a synergistic, coordinated way, placing both in the context of aberrant lateralization patterns.

Adult hippocampal neurogenesis (AHN) is crucial for the maintenance of hippocampal function. Several neurodegenerative diseases such as Alzheimer's disease (AD) are accompanied by memory deficits that could be related to alterations in AHN. Here, we took advantage of a conditional mouse model to study the involvement of glycogen synthase kinase-3β (GSK-3β) overexpression (OE) in AHN. By injecting GFP- and PSD95-GFP-expressing retroviruses, we have determined that hippocampal GSK-3β-OE causes dramatic alterations in both dendritic tree morphology and post-synaptic densities in newborn neurons. Alterations in previously damaged neurons were reverted by switching off the transgenic system and also by using a physiological approach (environmental enrichment) to increase hippocampal plasticity. Furthermore, comparative morphometric analysis of granule neurons from patients with AD and from GSK-3β overexpressing mice revealed shared morphological alterations. Taken together, these data indicate that GSK-3β is crucial for hippocampal function, thereby supporting this kinase as a relevant target for the treatment of AD.