More trials per condition: remove Medium

fMRI:

Targeting:

Visit 3, 4, 5 and 6: Online rTMS during the DRAT

Goal:• Enhance Working Memory manipulation performance in healthy subjects.

Visit 2: Imaging: T1, T2, DTI and fMRI

Goal:• Define individualized rTMS target using

fMRI activation associated with “difficulty” increase, during the delay period of the DRAT.

1Beynel L., 1Davis S.W., 1Crowell C.A., 1Hilbig S.A., 1Palmer H., 1Brito A., 1Hile, C., 1Lim, W., 1Nguyen, D., 1Dannhauer, M., 1Peterchev A.V., 1Cabeza R., 2Lisanby S.H., 2Luber B., & 1Appelbaum L.G.

1:Duke University, Durham, NC.

2:National Institute of Mental Health, Bethesda, MD.

Overall Methods:

Introduction:Working memory is the ability to perform mental operations on information that is stored in a flexible, limited capacity buffer. This ability is central to many aspects

of human cognition, but also declines with healthy aging. These 2 studies tested the capacity to enhance working memory manipulation with online repetitive transcranial magnetic stimulation (rTMS) in healthy young and older adults.

Site-specific effect of online repetitive transcranial magnetic stimulation (rTMS) on working memory (WM)

2P

- ** DTRP ** +

ITI (5s) Array (3s) Delay (5s) Probe (4s)

• Reorganize the letters into alphabetical order.• Indicate with button press if the number

correctly represents the serial position of the letter in the reorganized alphabetized order.

3P

2S

Valid

Invalid

New

Delayed Response Alphabetization Task (DRAT): Visit 1: Screening, resting motor threshold, DRAT practice

Goals: • Obtain motor threshold to define

TMS Intensity. • Define individually-titrated task difficulty

levels with 1-up-2-down staircase.

Frequency: 5Hz,Intensity: 100%rMT,Number of pulses per trial: 25,Control: electrical sham.

Study 2 – rTMS over the left Parietal cortex

Targeting: fMRI (Set Size * Sorting steps) + constrained mask

rTMS: On every trial:

Participants: 29YA + 18OA (no differences –> Collapsed).

Targeting: fMRI activations associated with increased set size correlated with E-field magnitude.

Participants: 17 OA

rTMS: Stim/Stim/No Stim:

Constrained Mask

Methods: Results: How to optimize this effect?

2P

- ** DTRP ** +

OR

• No difference on Stimulation Timing,• Accuracy Invalid trials < Accuracy Valid Trials,• Interaction between Difficulty and Stimulation, only

in the Invalid trials:

rTMS improves WM, only in the hardest condition

Parietal cortex

E-field Modeling: Coil orientation: 2nd phase of the E-field pointing perpendicularly into the closest sulcal wall

2P

- ** DTRP ** +

Methods: Results:• No differences between Invalid and Valid Trials,• Interaction between Difficulty and Stimulation:

rTMS disrupts WM, only in the hardest condition

Study 1 – rTMS over the left Dorso-Lateral Prefrontal cortex

F(1,14)=9.7, p= .008

p=.045

Conclusions:

While both frontal and parietal cortices belong to the same WM

network, online rTMS over these areas

led to opposite behavioral effects.

Site/Timing specific? Parietal cortex more involved

during the delay?

More research needed to understand these contradictory

results…

Meta-analysis of the effects of online rTMS on cognitive

functions (# P3.124)

[P3.123]