Memantine Augmentation in a Down's Syndrome Adolescent with Treatment- Resistant Obsessive-Compulsive Disorder

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140323/1/cap.2015.0073.pd

Topographic analysis of individual activation patterns in medial frontal cortex in schizophrenia

Individual variability in the location of neural activations poses a unique problem for neuroimaging studies employing group averaging techniques to investigate the neural bases of cognitive and emotional functions. This may be especially challenging for studies examining patient groups, which often have limited sample sizes and increased intersubject variability. In particular, medial frontal cortex (MFC) dysfunction is thought to underlie performance monitoring dysfunction among patients with schizophrenia, yet previous studies using group averaging to compare schizophrenic patients to controls have yielded conflicting results. To examine individual activations in MFC associated with two aspects of performance monitoring, interference and error processing, functional magnetic resonance imaging data were acquired while 17 patients with schizophrenia and 21 healthy controls (HCs) performed an event-related version of the multisource interference task. Comparisons of averaged data revealed few differences between the groups. By contrast, topographic analysis of individual activations for errors showed that control subjects exhibited activations spanning across both posterior and anterior regions of MFC while patients primarily activated posterior MFC, possibly reflecting an impaired emotional response to errors in schizophrenia. This discrepancy between topographic and group-averaged results may be due to the significant dispersion among individual activations, particularly in HCs, highlighting the importance of considering intersubject variability when interpreting the medial frontal response to error commission. Hum Brain Mapp, 2009. © 2008 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63054/1/20657_ftp.pd

Altered Activation Of The Rostral Anterior Cingulate Cortex In The Context Of Emotional Face Distractors In Children And Adolescents With Anxiety Disorders

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109274/1/da22289.pd

Neural correlates of explicit and implicit emotion processing in relation to treatment response in pediatric anxiety

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136676/1/jcpp12658_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136676/2/jcpp12658.pd

Impact of pubertal timing and depression on error‐related brain activity in anxious youth

Anxiety disorders are associated with enhanced error‐related negativity (ERN) across development but it remains unclear whether alterations in brain electrophysiology are linked to the timing of puberty. Pubertal timing and alterations of prefrontal and limbic development are implicated in risk for depression, but the interplay of these factors on the ERN–anxiety association has not been assessed. We examined the unique and interactive effects of pubertal timing and depression on the ERN in a sample of youth 10–19 years old with anxiety disorders (n = 30) or no history of psychopathology (n = 30). Earlier pubertal maturation was associated with an enhanced ERN. Among early, but not late maturing youth, higher depressive symptoms were associated with a reduced ERN. The magnitude of neural reactivity to errors is sensitive to anxiety, depression, and development. Early physical maturation and anxiety may heighten neural sensitivity to errors yet predict opposing effects in the context of depression.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146936/1/dev21763.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146936/2/dev21763_am.pd

Altered Relationship Between Electrophysiological Response to Errors and Gray Matter Volumes in an Extended Network for Error-Processing in Pediatric Obsessive-Compulsive Disorder

Abstract: Pediatric patients with obsessive-compulsive disorder (OCD) show an increased electrophysiological response to errors that is thought to be localized to the posterior medial prefrontal cortex (pMFC). However, the relation of this response, the error-related negativity (ERN), to underlying brain structures remains unknown. In an examination of 20 pediatric OCD patients and 20 healthy youth, we found that more negative ERN amplitude was correlated with lower gray matter (GM) density in pMFC and orbital frontal cortex. The association of the ERN with pMFC gray matter volume was driven by the patient group. In addition, a group difference in the association of ERN with gray matter in right insula was observed, showing an association of these measures in healthy youth (more negative ERN amplitude was associated with lower GM density in insula), but not in patients. These findings provide preliminary evidence linking gray matter volumes in an extended network for error processing to the ERN, and suggest that structural alterations in this network may underlie exaggeration of the ERN in pediatric OCD. Hum Brain Mapp 35:1143-1153

TLR4 activation induces IL-1ss release via an IPAF dependent but caspase 1/11/8 independent pathway in the lung

Background: The IL-1 family of cytokines is known to play an important role in inflammation therefore understanding the mechanism by which they are produced is paramount. Despite the recent plethora of publications dedicated to the study of these cytokines, the mechanism by which they are produced in the airway following endotoxin, Lipopolysaccharide (LPS), exposure is currently unclear. The aim was to determine the mechanism by which the IL-1 cytokines are produced after LPS inhaled challenge. Methods:Mice were challenged with aerosolised LPS, and lung tissue and bronchiolar lavage fluid (BALF) collected. Targets were measured at the mRNA and protein level; caspase activity was determined using specific assays. Results: BALF IL-1b/IL-18, but not IL-1a, was dependent on Ice Protease-Activating Factor (IPAF), and to a lesser extent Apoptosis-associated Speck-like protein containing a CARD (ASC). Interestingly, although we measured an increase in mRNA expression for caspase 1 and 11, we could not detect an increase in lung enzyme activity or a role for them in IL-1a/b production. Further investigations showed that whilst we could detect an increase in caspase 8 activity at later points in the time course (during resolution of inflammation), it appeared to play no role in the production of IL-1 cytokines in this model system. Conclusions: TLR4 activation increases levels of BALF IL-1b/IL-18 via an IPAF dependent and caspase 1/11/8 independent pathway. Furthermore, it would appear that the presence of IL-1a in the BALF is independent of these pathways. This novel data sheds light on innate signalling pathways in the lung that control the production of these key inflammatory cytokines

Chronic medication does not affect hyperactive error responses in obsessive-compulsive disorder

Patients with obsessive-compulsive disorder (OCD) show an increased error-related negativity (ERN), yet previous studies have not controlled for medication use, which may be important given evidence linking performance monitoring to neurotransmitter systems targeted by treatment, such as serotonin. In an examination of 19 unmedicated OCD patients, 19 medicated OCD patients, 19 medicated patient controls without OCD, and 21 unmedicated healthy controls, we found greater ERNs in OCD patients than in controls, irrespective of medication use. Severity of generalized anxiety and depression was associated with ERN amplitude in controls but not patients. These data confirm previous findings of an exaggerated error response in OCD, further showing that it cannot be attributed to medication. The absence in patients of a relationship between ERN amplitude and anxiety/depression, as was found in controls, suggests that elevated error signals in OCD may be disorder-specific.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79361/1/j.1469-8986.2010.00988.x.pd