Anomia Treatment Platform as Behavioral Engine for Use in Research on Physiological Adjuvants to Neurorehabilitation

The purpose of this study was to create a behavioral treatment engine for future use in research on physiological adjuvants in aphasia rehabilitation. We chose the behavioral target anomia, which is a feature displayed by many persons who have aphasia. Further, we wished to saturate the treatment approach with many strategies and cues that have been empirically reported to have a positive influence on aphasia outcome, with the goal being to optimize the potential for positive response in most participants. A single-subject multiple baseline design with replication across eight participants was employed. Four men and four women, with an average age of 62 yr and an average of 63.13 mo poststroke onset, served as participants. Word-retrieval treatment was administered 3 d/wk, 1 h/d for a total of 20 treatment hours (6-7 wk). Positive acquisition effects were evident in all eight participants (d effect size [ES] = 5.40). Treatment effects were maintained 3 mo after treatment termination for five participants (d ES = 2.94). Within and across semantic category, generalization was minimal (d ES = 0.43 within and 1.09 across). This study demonstrates that this behavioral treatment engine provides a solid platform on which to base future studies whereby various treatment conditions are manipulated and pharmacologic support is added

The Effects of Feature Type on Semantic Priming of Picture Naming in Normal Speakers

The aim of this study was to investigate the roles of features on conceptual activation.  A picture naming paradigm was employed to measure speech reaction time (SRT) during feature-to-concept activation.  Forty-seven older adults completed the priming task twice with an ISI of 200msec and 600msec. Results indicate that regardless of semantic category, distinctive feature primes resulted in the fastest SRT compared to shared features, combined distinctive and shared features, and neutral primes.  The results indicate that as stated in the Conceptual Structure Account (Tyler & Moss, 2001; Taylor et al., 2007) distinctive features have a privileged role in concept activation

Control of Chromatin by RNA-mediated Transcriptional Silencing

In multicellular eukaryotes, transposable elements (TE) make up a large part of the genomic content. These “selfish” genetic elements can propagate and expand the genome through their ability to replicate. However, this poses a significant risk to the stability of gene structure and overall genomic integrity which can lead to aberrant gene expression or products. To combat this threat, highly specific gene silencing mechanisms are utilized by the host to keep TEs in a constantly repressed state. In plants, transcriptional gene silencing is conducted through the RNA-directed DNA methylation (RdDM) pathway. The combined action of short interfering RNA (siRNA) and long non-coding RNA (lncRNA) direct deposition of DNA methylation at target TE regions. Subsequently, DNA methylation together with other repressive chromatin modifications turns the TE regions into a silenced state and prevent them from becoming active again. Although our understanding of the processes that lead up to the deposition of DNA methylation has been well-studied, the specific role and function of DNA methylation in gene silencing remains poorly understood. It is unclear how the presence of DNA methylation can affect the ability of transcription machinery from working at silenced regions. In contrast, DNA methylation does not hinder the transcriptional gene silencing machinery which suggests that DNA methylation plays a central role for distinguishing between different types of transcriptional activity in the DNA. In the first story, we determined how DNA methylation interacts with nucleosomes in the context of transcriptional silencing. DNA compaction and packaging in the nucleus entirely revolves around its interaction with nucleosomes. This interaction has numerous implications for regulation of gene expression through changes in accessibility of DNA to factors involved in transcription. Here we show that RdDM can direct both DNA methylation and nucleosome positioning. Nucleosomes established by RdDM have no detectable impact on DNA methylation. Instead, DNA methylation affects nucleosome positioning. This applies not only to CHH methylation established by RdDM but also to DNA methylation in CG and CHG contexts, which is maintained by MET1 and CMT3. We propose a model where DNA methylation serves as one of the determinants of nucleosome positioning. In the second story, we wanted to investigate the relationship between Pol V transcription and DNA methylation as a potential feedback mechanism where DNA methylation reinforces recruitment of Pol V transcription at silenced regions. Pol V transcribes in a pervasive manner throughout the genome implying that it does not require pre-existing chromatin marks such as DNA methylation to initiate transcription. However, previous studies have claimed that factors upstream of Pol V transcription that are able to bind to DNA methylation are required for the recruitment and initiation of Pol V transcription. Hence, the impact of DNA methylation on Pol V transcription remained unresolved. We found that loss of DNA methylation leads to a strong reduction of Pol V transcription. This occurs when DNA methylation is lost in all sequence contexts, which may happen not only in mutants defective in RdDM but also in mutants lacking maintenance DNA methyltransferases. Our results support a model where RdDM is maintained by a mutual reinforcement of DNA methylation and Pol V transcription with a strong crosstalk with other silencing pathways.PHDMolecular, Cellular, and Developmental BiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/169773/1/mrmhafiz_1.pd

Phonologic Rehabilitation of Anomia in Aphasia

The single most common feature of aphasia is impairment in ability to name, whether it involves naming seen objects, or producing nouns, verbs and other words conveying meaning in spontaneous language. The traditional treatment approach to this problem is to explicitly train aphasic patients in naming. Controlled studies have shown that this approach may be quite effective. However, typically generalization is very limited, that is, the knowledge gained by the patient tends to be limited to the words actually trained, and there is at best very modest improvement in performance with untrained words (limited mainly to those that are semantically related to the trained words). Because generalization is can be limited with this approach, there currently exists no viable means of training patients on the full corpus of words (perhaps several thousand) they are likely to need in daily life. Two approaches might be taken to solving this problem: 1) develop cost effective means for providing training on several thousand words; and 2) develop alternative training methods, e.g., phonological therapy, that potentially could intrinsically generalize widely. The focus of this proposal is the second of these two approaches. Thus, the primary purpose of this Phase II clinical rehabilitation study was to examine the effect of a phonologic based treatment on confrontation naming by individuals with anomic aphasia. We used a single-subject ABA design replicated across ten participants. The primary research question asked if phonologic treatment would improve confrontation naming. Secondary research questions addressed the impact of treatment on 1) generalization to untrained behaviors such as discourse production; 2) retention effects at 3-months; 3) phonologic production and 4) nonword repetition (potential evidence of phoneme sequence knowledge acquisition)

Neural Signatures of Semantic and Phonemic Fluency in Young and Old Adults

As we age, our ability to select and produce words changes, yet we know little about the underlying neural substrate of word-finding difficulties in old adults. The present study was designed to elucidate changes in specific frontally mediated retrieval processes involved in word-finding difficulties associated with advanced age. We implemented two overt verbal (semantic and phonemic) fluency tasks during functional magnetic resonance imaging and compared brain activity patterns of old and young adults. Performance during the phonemic task was comparable for both age-groups and mirrored by strongly left lateralized (frontal) activity patterns. On the other hand, a significant drop of performance during the semantic task in the older goup was accompanied by additional right (inferior and middle) frontal activity, which was negatively correlated with performance. Moreover, the younger group recruited different subportions of the left inferior frontal gyrus for both fluency tasks, while the older participants failed to show this distinction. Thus, functional integrity and efficient recruitment of left frontal language areas seems to be critical for successful word-retrieval in old age

Effects of Gesture and Semantic-Phonologic Treatments for Verb Retrieval

Evidence for verb retrieval treatment effects in aphasia is limited. In a within subject design, we compared effects of two verb retrieval treatments, semantic-phonologic training versus gesture training, in four individuals with verb retrieval impairments ranging from moderate to severe. Verb picture naming improved for trained verbs in three of four participants during semantic-phonologic training. Verb picture naming improved for trained verbs in only one of four participants during gesture training. No improvements were evident in untrained words during either training phase. Though verbs and gestures have closer neural correlates, there was greater advantage for semantic-phonologic training for verbs

Item Response Theory Analysis of the Western Aphasia Battery

The purpose of this investigation was to improve the validity of the Western Aphasia Battery for measuring aphasia severity and change over time by examining its fit to an item response theory (IRT) measurement model. The advantages of IRT include interval scaling, potential for equating scores across aphasia tests, and more veridical reporting of score reliability. Despite reasonable overall fit to the model, a small number of WAB items demonstrated substantial misfit, suggesting that they do not productively contribute to the measurement of aphasia severity. Potential explanations for this misfit, and implications of IRT for aphasia testing will be discussed

Attenuation of half sulfur mustard gas-induced acute lung injury in rats

Airway instillation into rats of 2-chloroethyl ethyl sulfide (CEES), the half molecule of sulfur mustard compound, results in acute lung injury, as measured by the leak of plasma albumin into the lung. Morphologically, early changes in the lung include alveolar hemorrhage and fibrin deposition and the influx of neutrophils. Following lung contact with CEES, progressive accumulation of collagen occurred in the lung, followed by parenchymal collapse. The co-instillation with CEES of liposomes containing pegylated (PEG)-catalase (CAT), PEG-superoxide dismutase (SOD), or the combination, greatly attenuated the development of lung injury. Likewise, the co-instillation of liposomes containing the reducing agents, N-acetylcysteine (NAC), glutathione (GSH), or resveratrol (RES), significantly reduced acute lung injury. The combination of complement depletion and airway instillation of liposomes containing anti-oxidant compounds maximally attenuated CEES-induced lung injury by nearly 80%. Delayed airway instillation of anti-oxidant-containing liposomes (containing NAC or GSH, or the combination) significantly diminished lung injury even when instillation was delayed as long as 1 h after lung exposure to CEES. These data indicate that CEES-induced injury of rat lungs can be substantially diminished by the presence of reducing agents or anti-oxidant enzymes delivered via liposomes. Copyright © 2005 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49522/1/1115_ftp.pd