TY - JOUR
T1 - Network-targeted stimulation engages neurobehavioral hallmarks of age-related memory decline
AU - Nilakantan, Aneesha S.
AU - Mesulam, M. Marsel
AU - Weintraub, Sandra
AU - Karp, Erica L.
AU - Vanhaerents, Stephen
AU - Voss, Joel L.
N1 - Funding Information:
This research was funded by the National Institute on Aging (T32AG20506, F31AG057109, R01AG049002) and a pilot project grant from the Northwestern University Cognitive Neurology and Alzheimer’s Disease Center (P30AG13854). None of the sponsoring organizations participated in the design, conduct, analysis, manuscript preparation, or decision to publish. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official view of the NIH.
Funding Information:
The authors thank Donna Bridge, Brennan Durr, Elise Gagnon, Melissa Gunlogson, Molly Hermiller, Sungshin Kim, Valerie McDonald, Melissa McSweeney, Jonathan O’Neil, Robert Palumbo, John Walker, Mallory Ward, and Kristen Warren for their support of this project. Neuroimaging was performed at the Northwestern University Center for Translational Imaging, supported by Northwestern University Department of Radiology. This research was also supported in part through the computational resources and staff contributions provided for Quest, the high-performance computing facility at Northwestern University, and by resources provided by Northwestern University Clinical and Translational Sciences Institute, funded by the National Center for Advancing Translational Sciences (UL1TR001422).
Publisher Copyright:
© American Academy of Neurology.
PY - 2019/5/14
Y1 - 2019/5/14
N2 - ObjectiveTo test whether targeting hippocampal-cortical brain networks with high-frequency transcranial magnetic stimulation in older adults influences behavioral and neural measures characteristic of age-related memory impairment.MethodsFifteen adults aged 64 to 80 years (mean = 72 years) completed a single-blind, sham-controlled experiment. Stimulation targets in parietal cortex were determined based on fMRI connectivity with the hippocampus. Recollection and recognition memory were assessed after 5 consecutive daily sessions of full-intensity stimulation vs low-intensity sham stimulation using a within-subjects crossover design. Neural correlates of recollection and recognition memory formation were obtained via fMRI, measured within the targeted hippocampal-cortical network vs a control frontal-parietal network. These outcomes were measured approximately 24 hours after the final stimulation session.ResultsRecollection was specifically impaired in older adults compared to a young-adult control sample at baseline. Relative to sham, stimulation improved recollection to a greater extent than recognition. Stimulation increased recollection fMRI signals throughout the hippocampal-cortical network, including at the targeted location of the hippocampus. Effects of stimulation on fMRI recollection signals were greater than those for recognition and were greater in the targeted network compared to the control network.ConclusionsAge-related recollection impairments were causally related to hippocampal-cortical network function in older adults. Stimulation selectively modified neural and behavioral hallmarks of age-related memory impairment, indicating effective engagement of memory intervention targets in older adults.
AB - ObjectiveTo test whether targeting hippocampal-cortical brain networks with high-frequency transcranial magnetic stimulation in older adults influences behavioral and neural measures characteristic of age-related memory impairment.MethodsFifteen adults aged 64 to 80 years (mean = 72 years) completed a single-blind, sham-controlled experiment. Stimulation targets in parietal cortex were determined based on fMRI connectivity with the hippocampus. Recollection and recognition memory were assessed after 5 consecutive daily sessions of full-intensity stimulation vs low-intensity sham stimulation using a within-subjects crossover design. Neural correlates of recollection and recognition memory formation were obtained via fMRI, measured within the targeted hippocampal-cortical network vs a control frontal-parietal network. These outcomes were measured approximately 24 hours after the final stimulation session.ResultsRecollection was specifically impaired in older adults compared to a young-adult control sample at baseline. Relative to sham, stimulation improved recollection to a greater extent than recognition. Stimulation increased recollection fMRI signals throughout the hippocampal-cortical network, including at the targeted location of the hippocampus. Effects of stimulation on fMRI recollection signals were greater than those for recognition and were greater in the targeted network compared to the control network.ConclusionsAge-related recollection impairments were causally related to hippocampal-cortical network function in older adults. Stimulation selectively modified neural and behavioral hallmarks of age-related memory impairment, indicating effective engagement of memory intervention targets in older adults.
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U2 - 10.1212/WNL.0000000000007502
DO - 10.1212/WNL.0000000000007502
M3 - Article
C2 - 30996057
AN - SCOPUS:85066163886
SN - 0028-3878
VL - 92
SP - E2349-E2354
JO - Neurology
JF - Neurology
IS - 20
ER -