title: Abnormal vocal behavior predicts executive and memory deficits in Alzheimer's disease.
abstract: Speakers respond automatically and rapidly to compensate for brief perturbations of pitch in their auditory feedback. The specific adjustments in vocal output require integration of brain regions involved in speech-motor-control in order to detect the sensory-feedback error and implement the motor correction. Cortical regions involved in the pitch reflex phenomenon are highly vulnerable targets of network disruption in Alzheimer's disease (AD). We examined the pitch reflex in AD patients (n = 19) compared to an age-matched control group (n = 16). We measured the degree of behavioral compensation (peak compensation) and the extent of the adaptive response (pitch-response persistence). Healthy-controls reached a peak compensation of 18.7 ± 0.8 cents, and demonstrated a sustained compensation at 8.9 ± 0.69 cents. AD patients, in contrast, demonstrated a significantly elevated peak compensation (22.4 ± 1.2 cents, p < 0.05), and a reduced sustained response (pitch-response persistence, 4.5 ± 0.88 cents, p < 0.001). The degree of increased peak compensation predicted executive dysfunction, while the degree of impaired pitch-response persistence predicted memory dysfunction, in AD patients. The current study demonstrates pitch reflex as a sensitive behavioral index of impaired prefrontal modulation of sensorimotor integration, and compromised plasticity mechanisms of memory, in AD.
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA, USA. Electronic address: kamalini.ranasinghe@ucsf.edu.
authors.forename: Kamalini G
authors.initials: KG
authors.lastname: Ranasinghe
authors.affiliation: Speech Neuroscience Laboratory, Department of Otolaryngology - Head and Neck Surgery, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Jeevit S
authors.initials: JS
authors.lastname: Gill
authors.affiliation: Speech Neuroscience Laboratory, Department of Otolaryngology - Head and Neck Surgery, University of California San Francisco, San Francisco, CA, USA; Biomagnetic Imaging Laboratory, Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Hardik
authors.initials: H
authors.lastname: Kothare
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Beagle
authors.affiliation: Biomagnetic Imaging Laboratory, Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Mizuiri
authors.affiliation: Biomagnetic Imaging Laboratory, Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Honma
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Gorno-Tempini
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA, USA; Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Vossel
authors.affiliation: Speech Neuroscience Laboratory, Department of Otolaryngology - Head and Neck Surgery, University of California San Francisco, San Francisco, CA, USA; Biomagnetic Imaging Laboratory, Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Srikantan S
authors.initials: SS
authors.lastname: Nagarajan
authors.affiliation: Speech Neuroscience Laboratory, Department of Otolaryngology - Head and Neck Surgery, University of California San Francisco, San Francisco, CA, USA; Biomagnetic Imaging Laboratory, Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA. Electronic address: houde@phy.ucsf.edu.
authors.forename: John F
authors.initials: JF
authors.lastname: Houde
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000503:physiopathology* / Q000523:psychology*; D056344:Executive Function; D056228:Feedback, Sensory / Q000502:physiology*; D005260:Female; D005544:Forecasting; D006801:Humans; D008297:Male; D008568:Memory; D008569:Memory Disorders / Q000503:physiopathology* / Q000523:psychology*; D008875:Middle Aged; D010898:Pitch Perception / Q000502:physiology*; D017397:Prefrontal Cortex / Q000503:physiopathology*; D012018:Reflex / Q000502:physiology*; D013060:Speech / Q000502:physiology*; D014705:Verbal Behavior / Q000502:physiology*
keywords: Alzheimer's disease; Executive dysfunction; Network disruption; Pitch perturbation; Prefrontal modulation; Sensorimotor integration