Efficacy of rTMS on Memory Enhancement in Older Adults with Traumatic Brain Injury: A Randomized Clinical Trial

Maheen Adamson, VA Palo Alto Health Care System, Palo Alto, United States
XJ Kang, VA Palo Alto Health Care System, Palo Alto, United States
Victoria Liou-Johnson, VA Palo Alto Health Care System, Palo Alto, United States
Dylan Jester, VA Palo Alto Health Care System, Palo Alto, United States
Daya Grewal, Palo Alto University, Palo Alto, United States
Daniel Baldini, Palo Alto University, Palo Alto, United States
Emily Dennis, University of Utah, Salt Lake, United States
Srija Seenivasan, Uniformed Services University, Bethesda, United States
Michael Zeineh, Stanford University, Stanford, United States
John Wesson Ashford, Palo Alto VA, Palo Alto, United States


A single blow to the head classified as a moderate or severe TBI is associated with progressive cognitive decline leading to dementia (reviewed in Lye & Shores, 2000; Smith et al., 2013). Immediate and delayed recall is often used to examine episodic memory in humans. It has been identified as one of the promising tests by the American Psychological Association (APA) to identify Alzheimer's disease (AD) before the symptoms appear (Spaan et al., 2005). In fact, hippocampal–whole brain connectivity–behavior relationships were not isolated to single networks, but spanned multiple brain networks and were unique for each behavioral measure. Repetitive transcranial magnetic stimulation (TMS) delivers therapeutic, non-invasive brain stimulation and is FDA-approved for treatment for major depression (George et al., 2010; O’Reardon et al., 2007). Repetitive TMS has also been used for memory enhancement (Wang et al., 2014). To date, no studies have examined rTMS treatment in older adults with a history of TBI. Here, a) To assess the efficacy of rTMS to predict improvement in memory performance pre and post rTMS intervention in older patients with TBI, and b) To assess hippocampal glucose uptake as a biomarker to detect these changes in memory performance.

Participants and Methods:

We enrolled (n=19) Veterans and civilians (mild and moderate TBI; mean age= 62.63) in either a placebo or an active trial arm. Participants were enrolled in a PET-MRI, and neuropsychological assessment at baseline, after 20 treatments (post-treatment), and six month follow-up. Participants were also involved in using CANTAB (spell out) and performed paired associate tasks at baseline, and post treatment and six months follow-up.

In a double-blind randomized clinical trial, we used rTMS (10 Hz) treatment on the left dorsolateral prefrontal cortex (LDLPFC) to improve memory problems in older adults with a history of TBI (for rtms delivery specifications see (Sultana et al., 2023)). . Specifically, functional neuronavigation based on resting state fMRI to locate the DLPFC.


Preliminary comparative analysis indicated significant differences (p<.05) on pre-post assessment in memory measures in the active group. Significant results were observed in immediate (p=0.003) and delayed (p=0.007) story memory recall and also paired associated memory tasks (p=0.05) in the active group, but not sham. The Active Mean Difference in PET in the hippocampus pre-post rTMS was higher than the Sham Mean Difference, but it did not reach significance. There was no correlation seen between the memory measures and PET activity in Active or Sham.


Despite the lower number of participants, due to COVID-19, a significant effect of rTMS treatment to LDLPFC in improving memory tasks was observed. This preliminary research highlights the importance of assessing memory paradigms that are directly correlated with cognitive decline and TBI-associated health problems in older adults and the treatments that can be used to mitigate them.

Category: Acquired Brain Injury (TBI/Cerebrovascular Injury and Disease - Adult)

Keyword 1: traumatic brain injury
Keyword 2: treatment outcome
Keyword 3: frontal lobes