Network-targeted stimulation engages neurobehavioral hallmarks of age-related memory decline

Abstract

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.

Episodic memory improvements due to noninvasive stimulation targeting the cortical–hippocampal network: A replication and extension experiment

“…Furthermore, the current findings do not support the proposal that increased episodic learning due to stimulation comes at the price of accelerated long‐term forgetting. Considered with other conceptual replications (Hermiller et al, ; Kim et al, ; Nilakantan et al, , ; Tambini et al, ), the current results support the notion that noninvasive stimulation targeting the hippocampal–cortical network can influence recollective memory tasks that are widely considered hippocampal‐dependent.…”

“…The current experiment also sought to address potential mechanisms whereby network-targeted stimulation improves memory. The effects of network-targeted stimulation on memory demonstrated in previous experiments (Kim et al, 2018;Nilakantan et al, 2017Nilakantan et al, , 2019Tambini et al, 2018;Wang & Voss, 2015) have been improvements in new learning ability. In these studies, the memory assessment involved learning a novel set of memoranda and then taking the memory test after a relatively brief delay (minutes to hours) on the same day.…”

“…The effects of stimulation on the targeted hippocampal–cortical network have been measured using memory testing and neuroimaging. There have been several demonstrations of improved recollection memory performance (Kim et al, ; Nilakantan et al, , ; Tambini et al, ; Wang et al, ) as well as corresponding changes in neuroimaging‐based measures of network function (Hermiller et al, ; Kim et al, ; Nilakantan et al, ; Wang et al, ). These experiments have therefore been important for identifying the role of hippocampal–cortical networks in memory.…”

“…These previous experiments have used different episodic memory outcomes, including cued recall of face‐word associates (Wang et al, ), spatial reconstruction (Nilakantan et al, ; Tambini et al, ), and paired‐associate recognition (Kim et al, ; Nilakantan et al, ). Findings that stimulation improved performance for these various test formats, all of which measure hippocampal‐dependent recollection, provide important conceptual replications of the phenomenon of improved episodic memory due to stimulation targeting the hippocampal–cortical network.…”

“…The distributed network of the human hippocampus includes regions such as the medial prefrontal, medial parietal, and lateral parietal cortex and is thought to support episodic memory (Buckner, Andrews-Hanna, & Schacter, 2008;Mesulam, 1990;Ranganath & Ritchey, 2012). Several experiments have tested contributions of the hippocampal-cortical network to memory using noninvasive brain stimulation (Hermiller, VanHaerents, Raij, & Voss, 2019;Kim et al, 2018;Nilakantan, Bridge, Gagnon, VanHaerents, & Voss, 2017;Nilakantan et al, 2019;Tambini, Nee, & D'Esposito, 2018;Wang et al, 2014). These experiments have used a network targeting approach, whereby transcranial magnetic stimulation (TMS) was applied to cortical regions defined based on their resting-state fMRI connectivity with the hippocampus.…”