Accurate integration of sensory inputs and motor commands is essential to achieve successful behavioral goals. A robust model of sensorimotor integration is the pitch perturbation response, in which speakers respond rapidly to shifts of the pitch in their auditory feedback. In a previous study, we demonstrated abnormal sensorimotor integration in patients with Alzheimer’s disease (AD) with an abnormally enhanced behavioral response to pitch perturbation. Here we examine the neural correlates of the abnormal pitch perturbation response in AD patients, using magnetoencephalographic imaging. The participants phonated the vowel /α/ while a real-time signal processor briefly perturbed the pitch (100 cents, 400 ms) of their auditory feedback. We examined the high-gamma band (65–150 Hz) responses during this task. AD patients showed significantly reduced left prefrontal activity during the early phase of perturbation and increased right middle temporal activity during the later phase of perturbation, compared to controls. Activity in these brain regions significantly correlated with the behavioral response. These results demonstrate that impaired prefrontal modulation of speech-motor-control network and additional recruitment of right temporal regions are significant mediators of aberrant sensorimotor integration in patients with AD. The abnormal neural integration mechanisms signify the contribution of cortical network dysfunction to cognitive and behavioral deficits in AD.
Bibliographical noteFunding Information:
We would like to thank all of the study participants and their families for their generous support to our research. This study was supported by grants from the Alzheimer’s Association: PCTRB-13-288476 [K.A.V.], ETAC-09-133596 [J.F.H., S.S.N.], grants from the National Institutes of Health: F32AG050434-01A1 [K.G.R.], K23 AG038357 [K.A.V.], P50 AG023501, P01 AG19724 [B.L.M.], R21 NS76171 [S.S.N.], R01EB022717 [S.S.N.] R01 DC010145 [J.F.H., S.S.N.], DC017696 [J.F.H., S.S.N.], DC013979 [J.F.H., S.S.N.], NS100440 [S.S.N., J.F.H., M.G.T.], National Science Foundation Grant BCS-1262297 [J.F.H., S.S.N.]; a grant from John Douglas French Alzheimer’s Foundation [K.A.V.]; a grant from Larry L. Hillblom Foundation, 2015-A-034-FEL [K.G.R.]; University of California San Francisco AD Research Center pilot project grant [K.A.V.]; a gift from Ricoh Inc. [S.S.N.]; and a gift from the S.D. Bechtel Jr. Foundation [K.A.V.].