Neural correlates of abnormal auditory feedback processing during speech production in Alzheimer’s disease

Kamalini G. Ranasinghe; Hardik Kothare; Naomi Kort; Leighton B. Hinkley; Alexander J. Beagle; Danielle Mizuiri; Susanne M. Honma; Richard Lee; Bruce L. Miller; Maria Luisa Gorno-Tempini; Keith A. Vossel; John F. Houde; Srikantan S. Nagarajan

doi:10.1038/s41598-019-41794-x

Neural correlates of abnormal auditory feedback processing during speech production in Alzheimer’s disease

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

Neurology

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

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.

Original language	English (US)
Article number	5686
Journal	Scientific reports
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41598-019-41794-x
State	Published - Dec 1 2019

Bibliographical note

Funding 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.].

Publisher Copyright:
© 2019, The Author(s).

Publisher link

10.1038/s41598-019-41794-x

Find It

Find It at U of M Libraries

Cite this

Ranasinghe, K. G., Kothare, H., Kort, N., Hinkley, L. B., Beagle, A. J., Mizuiri, D., Honma, S. M., Lee, R., Miller, B. L., Gorno-Tempini, M. L., Vossel, K. A., Houde, J. F., & Nagarajan, S. S. (2019). Neural correlates of abnormal auditory feedback processing during speech production in Alzheimer’s disease. Scientific reports, 9(1), Article 5686. https://doi.org/10.1038/s41598-019-41794-x

@article{eada4f467cc74d389513cb96b429c563,

title = "Neural correlates of abnormal auditory feedback processing during speech production in Alzheimer{\textquoteright}s disease",

abstract = "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{\textquoteright}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.",

author = "Ranasinghe, {Kamalini G.} and Hardik Kothare and Naomi Kort and Hinkley, {Leighton B.} and Beagle, {Alexander J.} and Danielle Mizuiri and Honma, {Susanne M.} and Richard Lee and Miller, {Bruce L.} and Gorno-Tempini, {Maria Luisa} and Vossel, {Keith A.} and Houde, {John F.} and Nagarajan, {Srikantan S.}",

note = "Funding 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{\textquoteright}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{\textquoteright}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.]. Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41598-019-41794-x",

language = "English (US)",

volume = "9",

journal = "Scientific reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Neural correlates of abnormal auditory feedback processing during speech production in Alzheimer’s disease

AU - Ranasinghe, Kamalini G.

AU - Kothare, Hardik

AU - Kort, Naomi

AU - Hinkley, Leighton B.

AU - Beagle, Alexander J.

AU - Mizuiri, Danielle

AU - Honma, Susanne M.

AU - Lee, Richard

AU - Miller, Bruce L.

AU - Gorno-Tempini, Maria Luisa

AU - Vossel, Keith A.

AU - Houde, John F.

AU - Nagarajan, Srikantan S.

N1 - Funding 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.]. Publisher Copyright: © 2019, The Author(s).

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85064045216&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064045216&partnerID=8YFLogxK

U2 - 10.1038/s41598-019-41794-x

DO - 10.1038/s41598-019-41794-x

M3 - Article

C2 - 30952883

AN - SCOPUS:85064045216

SN - 2045-2322

VL - 9

JO - Scientific reports

JF - Scientific reports

IS - 1

M1 - 5686

ER -

Neural correlates of abnormal auditory feedback processing during speech production in Alzheimer’s disease

Abstract

Bibliographical note

Publisher link

Find It

Other files and links

Fingerprint

Cite this