Targeted stimulation influences age-related changes in connectivity and function of hippocampal-cortical networks
Aneesha Nilakantan1, John Walker1, Sandra Weintraub1, Stephen VanHaerents1, Donna Bridge1, M-Marsel Mesulam1, Joel Voss1; 1Northwestern University
Healthy aging is associated with episodic memory decline, consistently correlated with altered hippocampal-cortical connectivity at rest and abnormal hippocampal activity during memory formation. Here, we used noninvasive repetitive transcranial magnetic stimulation (rTMS) to test the causal role of hippocampal-cortical network connectivity in age-related memory decline. Subject-specific left parietal stimulation locations were determined based on their resting-state fMRI connectivity with the body of the hippocampus. In a counter-balanced order, participants (n=14, age range: 60-80 years) were given five consecutive days of full intensity (20Hz) stimulation and five consecutive days of low intensity stimulation (sham). fMRI was collected both at rest and during an associative memory task, involving the recall of 36 object-scene pairs, administered before and 24-hours after each five-day stimulation period. At baseline, older adults showed significantly decreased hippocampal connectivity with medial prefrontal and parahippocampal cortex, and increased hippocampal connectivity with posterior cingulate, precuneus, and parietal cortex, relative to young adults (n=16, age range: 18-34 years). Targeted stimulation significantly decreased the age-related hippocampal hyper-connectivity in the posterior cingulate, relative to sham. Similarly, targeted stimulation decreased posterior cingulate activity and increased hippocampal activity during memory formation. Importantly, these changes in connectivity and task-evoked processing were concurrent with an improvement in associative scene recollection, but not in object recognition. These findings suggest that changes in hippocampal memory network function are causally related to episodic memory impairment in aging, and demonstrate that noninvasive stimulation can be used to alter memory-related network function in older adults.
Topic Area: LONG-TERM MEMORY: Episodic