Longitudinal cerebral blood flow changes during speech in hereditary ataxia

Abstract

The hereditary ataxias constitute a group of degenerative diseases that progress over years or decades. With principal pathology involving the cerebellum, dysarthria is an early feature of many of the ataxias. Positron Emission Tomography was used to study regional cerebral blood flow changes during speech production over a 21 month period in a group of seven right-handed subjects with hereditary ataxia (6 females and 1 male, 3 SCA1 and 4 SCA5, aged 38.3 +/− 18.9 years). The decline in blood flow was greatest in cerebellar regions. In contrast, blood flow actually increased during speech production in the classic speech area (Broca’s area) but not in its right hemisphere homologue at the second evaluation. This increase in cortical flow may have been compensatory for cerebellar degeneration as speech intelligibility did not decline significantly during this period. Compensation was not complete, though, as syllable timing shifted in the direction of equal syllable duration, one of the characteristics of ataxic dysarthria. These results are consistent with previous functional imaging studies of ataxia demonstrating a pattern of brain activity that reflects both loss of function and relative compensation when clinical signs and symptoms are still mild. The combination of disease-relevant tasks, behavioral measurement, and functional imaging may provide insight into the early changes associated with neurodegenerative disease.

Spatiotemporal linear mixed effects modeling for the mass-univariate analysis of longitudinal neuroimage data

“…(Asami et al, 2011; Blockx et al, 2011; Chetelat et al, 2005; Davatzikos and Resnick, 2002; Desikan et al, 2011; Draganski et al, 2004; Driscoll et al, 2011; Fjell et al, 2009; Fotenos et al, 2005; Fouquet et al, 2009; Frings et al, 2011; Giedd et al, 1999; Hedman et al, 2011; Ho et al, 2003; Holland et al, 2009; Holland et al, 2011; Hua et al, 2010; Hua et al, 2009; Jack Jr et al, 2009; Jack Jr et al, 2008; Josephs et al, 2008; Kaladjian et al, 2009; Kalkers et al, 2002; Ment et al, 2009; Misra et al, 2009; Pantelis et al, 2003; Paviour et al, 2006; Resnick et al, 2010; Sabuncu et al, 2011; Schuff et al, 2010; Schumann et al, 2010; Sidtis et al, 2010; Sluimer et al, 2008; Sluimer et al, 2009; Sullivan et al, 2011; Thambisetty et al, 2011; Thambisetty et al, 2010; Whitwell et al, 2011; Whitwell et al, 2007), most LNI studies have either focused on a small number of image measurements via univariate analyses and/or utilized methods that are suboptimal for detecting longitudinal effects (Bernal-Rusiel et al, 2012). The reduction in statistical power due to suboptimal methodology is particularly detrimental when exploring brain-wide associations in a mass-univariate fashion .…”

Speech characteristics associated with three genotypes of ataxia

“…However, to increase our sensitivity to potential genotypic differences across a range of severity, we have also included annual follow-up data on a subset of subjects who were followed for up to three years. In a previous PET study, these subjects demonstrated progressive declines of cerebellar blood flow and changes in speech timing over the period of study (Sidtis, Strother, Groshong, Rottenberg, & Gomez, 2010). As a complex of neurologic signs and symptoms that varies with SCA type, the concept of severity in ataxia is not straightforward.…”

“…A longitudinal study of our SCA subjects who were identified prior to significant symptom onset examined changes in regional cerebral blood flow and speech (Sidtis, Strother, Groshong, Rottenberg, & Gomez, 2010). Over a two year period, speech timing shifted towards equal intervals in a syllable repetition task (pa-ta-ka), and blood flow was reduced in the cerebellum but increased in Broca’s area.…”

“…The present study was undertaken to examine the clinical characteristics of the speech of individuals from three genotypes of SCA who participated in studies of brain activity during speech (Sidtis et al, 2006; 2010), and to further determine if specific speech abnormalities could be associated with each SCA type. Given the limited knowledge of possible differences in disordered speech across the newly identified genotypes of SCA, this is a descriptive study.…”

“…Five of the speakers had second annual follow-up evaluations (3 SCA1 and 2 SCA5) and one of these (1 SCA1) had a third annual follow-up evaluation. The SCA subjects with follow-up examinations entered the study at a very early stage of their disease but were found to have significant changes in their speech and brain function over the course of follow-up (Sidtis, Strother, Groshong, Rottenberg, & Gomez, 2010). As SCA is progressive disease, the follow-up evaluations were included in this study to capture a wider range of severity within SCA types.…”