Summary: Transcranial magnetic stimulation (TMS) applied to a parietal site that is tightly connected to the hippocampus restores activity in memory-related brain networks and improves associative memory in older adults with age-related decline, bringing performance up to the level of younger adults.
Source: Northwestern University
Targeted electromagnetic pulses to a precise cortical site connected with the hippocampus improved memory in older adults with age-related decline, according to a new Northwestern Medicine study.
“Older people’s memory improved to the point that we could no longer distinguish their performance from that of younger participants,” said lead investigator Joel Voss, associate professor at Northwestern University Feinberg School of Medicine. “The change was substantial.”
The researchers applied Transcranial Magnetic Stimulation (TMS) to a parietal region functionally connected to the hippocampus, the deep brain structure that typically shrinks with age and is critical for forming associative memories.
The study is scheduled for publication April 17 in Neurology.
“The hippocampus helps bind separate elements into a single memory, like where you left your keys or a new neighbor’s name,” Voss explained. “Many older adults report difficulty with this type of remembering.”
Associative memory—the ability to link unrelated items—declines with normal aging, and most people experience some degree of memory change over time.
This experiment enrolled 16 adults aged 64 to 80 who had normal, age-related memory impairments. The results show that it is possible to modify memory ability in older adults using network-targeted TMS, Voss said. “Until now, there has been no clear evidence that the specific memory deficits and network dysfunction typical of aging could be rescued with brain stimulation or other interventions.”
Before stimulation, the team used functional MRI (fMRI) to identify each participant’s hippocampus and to find an overlying cortical site in the parietal lobe that showed strong functional connectivity with the hippocampus. That cortical target—located behind and slightly above the left ear in most people—varied slightly for each individual.
Because the hippocampus lies too deep for TMS to reach directly, the investigators stimulated a superficial, connected cortical region. “We stimulated sites whose activity was synchronized with the hippocampus, indicating that those areas communicate with it,” said first author Aneesha Nilakantan, a neuroscience graduate student in Voss’ lab.
At baseline, participants completed associative memory tasks that required learning arbitrary pairings—for example, placing an object in a matching location on a computer screen. Younger adults typically scored around 55 percent correct on these tasks, while older adults scored under 40 percent.
The intervention consisted of high-frequency, repetitive TMS applied to each person’s individualized parietal target for 20 minutes per day over five consecutive days. fMRI taken after stimulation showed increased activity across hippocampal-cortical memory networks, indicating enhanced function in regions that normally show age-related disruption.
Approximately 24 hours after the last stimulation session, participants took a new associative memory test. Older adults who received the full-intensity TMS performed at levels comparable to the younger control group. A sham (placebo) stimulation condition was included and did not produce similar benefits.
The investigators will next evaluate this network-targeted stimulation approach in people with mild cognitive impairment, an early stage of Alzheimer’s disease, and will test longer courses of stimulation. Voss cautioned that the duration of the memory benefits remains unclear. He noted, however, that in depression treatment, TMS protocols delivered over five weeks can produce effects that last for months, and he plans studies with extended stimulation schedules to assess durability in age-related memory loss.
Funding: This research was supported in part by the National Institute on Aging through grants T32AG20506, F31AG057109 and R01AG049002 of the National Institutes of Health.
Source:
Northwestern University
Media Contacts:
Marla Paul – Northwestern University
Image Source:
The image is adapted from the Northwestern University news release.
Original Research: Closed access.
“Network-targeted stimulation engages neurobehavioral hallmarks of age-related memory decline”
Aneesha S. Nilakantan, M.-Marsel Mesulam, Sandra Weintraub, Erica L. Karp, Stephen VanHaerents, Joel L. Voss. Neurology doi: 10.1212/WNL.0000000000007502
Abstract
Network-targeted stimulation engages neurobehavioral hallmarks of age-related memory decline
Objective: To determine whether high-frequency TMS targeting hippocampal-cortical networks in older adults alters behavioral and neural measures associated with age-related memory impairment.
Methods: Fifteen adults aged 64 to 80 (mean = 72) completed a single-blind, sham-controlled crossover experiment. Parietal stimulation targets were individualized using fMRI connectivity to the hippocampus. Recollection and recognition were measured after five consecutive daily sessions of full-intensity stimulation versus low-intensity sham. Neural correlates of memory formation were assessed via fMRI within the targeted hippocampal-cortical network compared with a frontal-parietal control network. Outcomes were measured about 24 hours after the final stimulation session.
Results: Baseline testing revealed recollection deficits in older adults relative to a young-adult sample. Relative to sham, stimulation selectively improved recollection more than recognition and increased recollection-related fMRI signals across the hippocampal-cortical network, including the hippocampal target. Stimulation effects were stronger for recollection than recognition and were greater in the targeted network than in the control network.
Conclusions: Age-related recollection impairments are causally linked to hippocampal-cortical network dysfunction. Network-targeted TMS selectively modified neural and behavioral features of age-related memory decline, demonstrating effective engagement of memory-relevant targets in older adults.