Individualized Closed Loop TMS for Working Memory Enhancement


The study is investigating working memory brain states by using transcranial magnetic stimulation (TMS) in combination with functional magnetic resonance imaging (fMRI). The study uses a novel, individualized targeting approach for TMS based on each subject's individual multi-modal fMRI data. Next, the individualized target will be stimulated in a TMS/ fMRI imaging session to investigate working memory states and optimal stimulation frequencies.

Full Title of Study: “Individualized Closed Loop Transcranial Magnetic Stimulation (TMS) for Working Memory Enhancement”

Study Type

  • Study Type: Interventional
  • Study Design
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Basic Science
    • Masking: Double (Participant, Care Provider)
  • Study Primary Completion Date: January 2024


  • Device: Repetitive Transcranial Magnetic Stimulation (rTMS)
    • The investigators will create individualized TMS targets using deep learning methods on task and resting fMRI data to target working memory augmentation. The individualized target will be stimulated in a subsequent fMRI scan involving working memory task performance interleaved with repetitive TMS (rTMS) delivered at a variety of stimulation frequencies. Based on activation readouts in response to rTMS, an optimal and sub-optimal brain state frequency to impact working memory performance will be selected for each participant. Participants will receive rTMS at each frequency separately for three days (six days total), with the order of frequency randomly assigned and counterbalanced. Following each three day protocol, another fMRI working memory readout will be conducted to support the targeting and frequency selection algorithms.

Clinical Trial Outcome Measures

Primary Measures

  • fMRI Classifier Fit
    • Time Frame: Baseline
    • Using deep learning classification methods, an ‘optimal’ brain state will be identified from baseline task and resting fMRI. This will be the target during future interleaved TMS/fMRI brain readouts.
  • Effect of Individualized Stimulation Frequency on Working Memory
    • Time Frame: Baseline, Immediately After the Intervention
    • Overall, the investigators will be assessing whether there is a significant change in working memory performance using neuromodulation at the individual’s optimal stimulation frequency versus sub-optimal frequency, as determined by performance during fMRI/ rTMS sessions and rTMS behavioral sessions.

Secondary Measures

  • Working Memory Performance in MRI Sessions
    • Time Frame: Baseline, After approx. 1 month, After approx. 2 months
    • During rounds of interleaved rTMS with fMRI recordings, participants will be engaging in a working memory task. Online block-wise performance will be evaluated for both speed and accuracy as an indicator of the effect of the neuromodulation train preceding it.
  • Working Memory Performance in Behavior Sessions
    • Time Frame: Baseline, Immediately after the Intervention
    • During each offline working memory rTMS session, participants’ speed and accuracy on a working memory task will be evaluated as an indicator of the degree to which the neuromodulation is affecting performance.

Participating in This Clinical Trial

Inclusion Criteria

  • 18-60 years old
  • Right handed
  • No current or lifetime history of any DSM-V diagnosis
  • No history of neurological disorder or traumatic brain injury (other than mild)
  • No current psychoactive medication use
  • Normal cognition
  • Female patients must attest to not being pregnant
  • Capacity to give informed consent and follow study procedures
  • Sufficient command of English language to understand and respond to written as well as verbal instructions

Exclusion Criteria

  • Unable to have an MRI scan, including current or prior medical condition that could interfere with the collection or interpretation of MRI data
  • Implanted devices, such as an aneurysm clip or cardiac pacemaker
  • History of stroke, epilepsy, or brain scarring
  • Cognitive impairment
  • Recent use of psychoactive medications, as determined by investigators
  • People who are unwilling/unable to abstain from medications that substantially reduce the seizure threshold to TMS under PI discretion
  • Otherwise determined by investigator to be unfit for study.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 60 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • University of Pennsylvania
  • Provider of Information About this Clinical Study
    • Sponsor

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