Faculty Bibliography

Background: Repetition occurs plentifully in normal conversation, but empirical studies of the pragmatic use of repetition are rare and pragmatic repetition, defined as verbal repetition in conversational use, in disordered language has not been systematically investigated. Applying a method of analysis that was piloted utilising normal discourse, discourse samples from persons with left and right brain damaged were examined for incidence and charcteristics of repetition. Aims: The purpose of this exploratory study was to examine verbal repetition following cerebral hemispheric damage. From previous studies of hemispheric influences on communicative competence, it was hypothesised that unilateral damage would affect verbal repetition differently. Following earlier results for hemispheric effects on proportion of formulaic expressions, overall more verbal repetition was predicted in persons with left hemisphere damage than those with right hemisphere damage or healthy speakers. Furthermore, previous studies led to a prediction of more repetition of formulaic (than novel, propositional) expressions following left hemisphere damage than the other two study groups. We explored whether characteristics and functions of repetition, developed as part of a new method for quantifying repetition in spontaneous speech, differed systematically between groups. Methods & Procedures: Transcripts of discourse by persons diagnosed with a single cerebral vascular accident and from age- and education-comparable healthy control (HC) participants were analysed. A method was developed for quantifying verbal repetition and identifying five factors, specifically localness (immediate, delayed, or distant), preservation of the original target (identical or altered), source (self or other), grammatical unit of speech (word, phrase, clause, or sentence), and phrase type (formulaic or novel), and three functions (maintaining form, enhancing content, and socialisation). Outcomes & Results: Results revealed significantly high!

The corpus callosum (CC) is the largest fiber bundle connecting the left and right cerebral hemispheres. It has been a region examined extensively for indications of various pathologies, including Alzheimer's disease (AD). Almost all previous studies of the CC in AD have been concerned with its size, particularly its mid-sagittal cross-sectional area (CCA). In this study, we show that the CC shape, characterized by its circularity (CIR), may be affected more profoundly than its size in early AD. MRI scans (n = 196) were obtained from the publicly available Open Access Series of Imaging Studies database. The CC cross-sectional region on the mid-sagittal section of the brain was automatically segmented using a novel algorithm. The CCA and CIR were compared in 98 normal controls (NC) subjects, 70 patients with very mild AD (AD-VM), and 28 patients with mild AD (AD-M). Statistical analysis of covariance controlling for age and intracranial capacity showed that both the CIR and the CCA were significantly reduced in the AD-VM group relative to the NC group (CIR: p = 0.004; CCA: p = 0.005). However, only the CIR was significantly different between the AD-M and AD-VM groups (p = 0.006) being smaller in the former. The CCA was not significantly different between the AD-M and AD-VM groups. The results suggest that CC shape may be a more sensitive marker than its size for monitoring the progression of AD. In order to facilitate independent analyses, the CC segmentations and the CCA and CIR data used in this study have been made publicly available ( http://www.nitrc.org/projects/art ).

The present study examined pausing patterns in spontaneous speech as a measure of the effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on parkinsonian speech. Pauses reflect various aspects of speech and language processes, including motor initiation and linguistic planning. Relatively little attention has been given to pauses in determining the effect of STN-DBS. An examination of pausing may be helpful to understanding how this form of therapy affects these behaviors. Seven individuals with Parkinson's disease who received surgery for bilateral STN-DBS participated. Spontaneous speech samples were elicited in both the ON and OFF STN-DBS condition. Findings indicated that long pauses (250-3000 ms) in spontaneous speech were significantly shorter and more frequent in the STN-DBS ON condition. Furthermore, the proportion of nonlinguistic boundary pauses was significantly greater with stimulation. The findings support previous studies suggesting that speech motor control and lexical retrieval may be affected by STN-DBS.

Background: Alzheimer's disease (AD) has been shown to be associated with shrinkage of the corpus callosum mid-sagittal cross-sectional area (CCA). Objective: To study temporal rates of corpus callosum atrophy not previously reported for early AD. Methods: We used longitudinal MRI scans to study the rates of change of CCA and circularity (CIR), a measure of its shape, in normal controls (NC, n = 75), patients with very mild AD (AD-VM, n = 51), and mild AD (AD-M, n = 21). Results: There were significant reduction rates in CCA and CIR in all three groups. While CCA reduction rates were not statistically different between groups, the CIR declined faster in AD-VM (p < 0.03) and AD-M (p < 0.0001) relative to NC, and in AD-M relative to AD-VM (p < 0.0004). Conclusion: CIR declines at an accelerated rate with AD severity. Its rate of change is more closely associated with AD progression than CCA or any of its sub-regions. CIR may be a useful group biomarker for objective assessment of treatments that aim to slow AD progression.

Background: An upregulation of monocyte chemoattractant protein-1 (MCP-1) and other chemokines (Interleukin-8 [IL-8] and Interferon gamma-induced protein 10 [IP-10]) has been reported in MCI and mild Alzheimer's disease (AD). MCP-1 is one of the key chemokines that regulate migration and infiltration of monocytes/macrophages. In AD, higher CSF MCP-1, and IP-10 have been associated with higher MMSE scores, suggesting potential beneficial effects of chemokine upregulation. This may include possible effects on AD biomarkers (Abeta and tau indices), which are known to be implicated in preclinical AD. This study examined the relationship between CSF chemokine levels and established AD biomarkers in older individuals with Major Depressive Disorder (MDD), which is a risk factor for AD, and in healthy controls. Methods: CSF was obtained from 47 older subjects with intact cognition and a Mini-Mental State Exam score of at least 28; 29 with MDD and 19 controls. MRI scans were performed to rule out structural brain abnormalities. No subject had gross MRI abnormalities other than white matter hyperintensities. CSF MCP-1, IP-10, IL-8, were determined using Luminex Corporation multiplexed beadbased immunoassays. Abeta40, Abeta42, total-tau, and ptau were determined using previously published methods. Results: MCP-1 was negatively correlated with CSF Abeta40 (r=-0.376, p=0.011), total tau (r=-0.361, p=0.014), and p-tau (r=-0.361, p=0.014); IL-8 was positively correlated with t-tau (r=0.357, p=0.015); IP-10 was positively correlated with t-tau (r=0.380, p=0.009) and p-tau (r=0.323, p=0.027). None of the chemokines showed a significant correlation with Abeta42 or significant group differences. Conclusions: Our findings suggest complex and differential associations between these chemokines and CSF AD Abeta and tau indices and highlight the need for further studies to determine their prognostic significance

The role of subcortical structures in language function is complex and dependent on language task, with studies increasingly showing subcortical involvement for the production of formulaic language, including recited speech. Individuals with Parkinson's disease (PD), with (n = 6) and without (n = 7) surgical treatment, deep brain stimulation (DBS), were compared to healthy adults (n = 14) to determine whether individuals with subcortical dysfunction produce more errors during a recitation speech task. Participants were asked to recite poems, prayers, and rhymes familiar to them in order to determine the effects of subcortical disease on recited speech ability. When compared with healthy controls, the DBS-OFF group produced significantly more error words, suggesting that deficits in recitation arise with severe states of subcortical dysfunction. Individuals with DBS in the ON or OFF conditions did not differ significantly during the recited speech task. Results support a model of language where large units of overlearned language are at least partially modulated by subcortical structures.

A number of studies have reported that, "relative to brain size," the midsagittal corpus callosum cross-sectional area (CCA) in females is on average larger than in males. However, others suggest that these may be spurious differences created in the CCA-to-brain-size ratio because brain size tends to be larger in males. To help resolve this controversy, we measured the CCA on all 316 magnetic resonance imaging (MRI) scans of normal subjects (18-94 years) in the OASIS (Open Access Series of Imaging Studies) cross-sectional dataset, and used multiple regression analysis to statistically control for the confounding effects of brain size and age to test the null hypothesis that the average CCA is not different between genders. An additional analysis was performed on a subset of 74 young adults (37 males and 37 females; 18-29 years) matched closely to brain size. Our null hypothesis was rejected in both analyses. In the entire sample (n= 316), controlling for brain size and age, the average CCA was significantly (P< 0.03) larger in females. The difference favoring females was more pronounced in the young adults cohort (P< 0.0005). These results provide strong additional evidence that the CCA is larger in females after correcting for the confounding effect of brain size.

One of the cognitive changes associated with Alzheimer's disease is a diminution of the primacy effect, i.e., the tendency toward better recall of items studied early on a list compared with the rest. We examined whether learning and recall of primacy words predicted subsequent cognitive decline in 204 elderly subjects who were non-demented and cognitively intact when first examined. Our results show that poorer primacy performance in the Rey Auditory Verbal Learning Test delayed recall trials, but not in immediate recall trials, is an effective predictor of subsequent decline in general cognitive function. This pattern of performance can be interpreted as evidence that failure to consolidate primacy items is a marker of cognitive decline.

BACKGROUND: Initial shortening of stem vowels in three-word derivational paradigms (e.g., zip, zipper, zippering) was studied in persons with Parkinson's disease (PWPD) with and without deep brain stimulation (DBS), and in normal speakers. METHOD: Seven PWPD without DBS, 7 PWPD with DBS ON (DBSN) or OFF (DBSF), and 6 healthy control (CON) persons were studied. Stimuli were 7 three-word paradigms consisting of a stem word and two derived longer forms created by adding the suffixes er (+1), and er+ing (+2). RESULTS: Vowel durations decreased across word forms of increasing length (initial shortening) for DBSF, DBSN, PWPD, and CON. Vowel shortening did not interact with group. For each word form, CON vowel duration was shorter than those for PWPD, DBSN and DBSF but word duration did not differ between groups. DBS did not have a significant effect on either vowel or word duration. CONCLUSION: These results agree with previous findings for a PWPD with accelerated speech and faster rates of speech in DBS-ON. Observations that vowel duration patterns are maintained in subcortical and cerebellar but not left hemisphere damage suggest that cortical control factors play a primary role in relational timing.