Auditory Feedback Processing in Alzheimer’s disease

Kamalini Ranasinghe, Dept. of Neurology, UCSF, San Francisco, CA

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 studied the neural and behavioral responses of pitch-reflex in AD patients (n=19) compared to an age-matched control group (n=16). Subjects phonated the vowel /a/ while a real-time signal processor briefly perturbed (±100 Cent for 400ms) pitch of their auditory feedback. We measured the degree of behavioral compensation (peak-compensation) and the extent of the adaptive response (pitch-response-persistence), and used magnetoencephalography to record the high-gamma band (65 – 150 Hz) evoked response during pitch-reflex. 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). In AD patients, the degree of increased peak-compensation predicted executive dysfunction, while the degree of impaired pitch-response-persistence predicted memory dysfunction. Neural analysis revealed that, AD patients show a significant reduced prefrontal activity during the early phase of the response, and a significantly enhanced left premotor and posterior temporal activity throughout the response period, compared to age-matched controls. These results implicate the lack of sensory-motor network modulation of speech-motor-control network in AD during auditory feedback control of pitch. The current study also demonstrates that pitch-reflex is a sensitive behavioral index of impaired prefrontal modulation of sensorimotor integration, and compromised plasticity mechanisms of memory, in AD.