Kamalini G Ranasinghe, Hardik Kothare, Naomi Kort, Leighton B. Hinkley, Alexander J Beagle, Danielle Mizuiri, Susanne M Honma, Bruce L Miller, Keith A Vossel, John F Houde, Srikantan S Nagarajan

Accurate integration of sensory inputs and motor commands is essential to achieve successful behavioral goals. In a previous study we demonstrated impaired sensorimotor integration in patients with Alzheimer’s disease (AD) with an abnormally increased pitch reflex compared to controls. In this study we examined the neural correlates of the abnormal pitch reflex. We examined the high-gamma band (65–150Hz) neural responses using magnetoencephalography and their specific correlates to behavioral response, as the participants (n=16, patients; n=13, age-matched controls) phonated the vowel /a/ while a real-time signal processor briefly perturbed (100 cents for 400 ms) the pitch of their auditory feedback. We found that AD patients show significantly reduced left prefrontal activity during the early phase and increased right middle temporal activity during the later phase, of the pitch reflex, compared to controls. The left prefrontal  and right middle temporal activity significantly predicted the degree of peak behavioral response in pitch reflex. The left prefrontal and right middle temporal high-gamma band activity showed significant independent associations with the peak behavioral response when controlled for the degree of executive function abilities, global cognitive performance and age. Furthermore, the high-gamma activity of the left prefrontal cortex was significantly correlated with the degree of executive function abilities, after regressing on the peak behavioral response, in the combined cohort of patients and controls. These results demonstrate the neural substrates of the abnormal pitch reflex in patients with AD and identify the neural circuit dysfunctions that may likely impact both low-level sensorimotor and high-level executive functions in AD.